REUSABLE SOLID SUPPORT FOR OLIGONUCLEOTIDE SYNTHESIS

Abstract: A reusable linker arm for solid support oligonucleotide synthesis, the linker arm comprising formula (a) wherein Z is a linker moiety and T is an organic radical. A method for adding one or more nucleosides on the linker arm is also described.

Description: REUSABLE SOLID SUPPORT FOR OLIGONUCLEOTIDE SYNTHESIS TECHNICAL FIELD In one of its aspects, the present invention relates to a reusable solid support for oligonucleotide synthesis. In another of its aspects, the present invention relates to a process for production of such a reusable solid support. In yet another of its aspects, the present invention relates to a process for use of such a reusable solid support. BACKGROUND ART The art of organic chemistry on solid supports is generally known. A useful review article on this topic may be found in "Organic Chemistry on Solid Supports" by Friichtel et al, Angew. Chem. Int. Ed. Engl, 1996, 35, pgs. 17-42, the contents of which are hereby incorporated by reference. As discussed in Friichtel et al., the art has developed automated solid- phase synthesis of polypeptides, oligonucleotides and oligosaccharaides. Of particular interest here is solid-phase synthesis of oligonucleotides. The following are useful review articles/textbooks on this topic: Beaucage et al., Tetrahedron, 1992, 48, 2223; Davis et al., Innovation and Perspectives in Solid Phase Synthesis (Ed.: R. Epton), Intercept, Andover, 1992, pg. 63; Montserra et al., Tetrahedron, 1994, 50, 2617; and S. L. Beaucage et al, Tetrahedron, 1993, 49, 6123-6194; the contents of each of which are hereby incorporated by reference. In the solid-phase synthesis of oligonucleotides, it is known to synthesize the oligonucleotide on an inorganic solid support bearing a succinyl linker arm - see, for example, any of the following references: Caruthers et al., Genetic Engineering, Plenum Press, New York (1982), Vol. 4, pgs 1-17, Letsmger et al., Genetic Engineering, Plenum Press. New York (1985), Vol 5, pg 191, Matteucci et al., Journal of American Chemical Society, 103:3185-3186 (1981), the contents of each of which are hereby incorporated by reference. Typically, the succinyl linker arm has the following general formula: Thus, the succmyl group links the growing oligonucleotide from its terminal 3' hydroxyl group by an ester bond to a pπmary amme on the support, which may be, for example, conventional controlled pore glass (CPG) or silica, by an amide bond. Once the desired oligonucleotide has been synthesized, it is freed or cleaved from the succinyl linker arm hydrolyzmg the ester carbonyl group. The hydrolysis agent is usually concentrated ammonium hydroxide Typically, this reaction can take from 1 -4 hours to complete. With improvements to current solid-phase oligonucleotide synthesizers, this cleavage step can represent 50% or more of the total time require to synthesize the desired oligonucleotide. Another type of linker arm is disclosed in United States patent 5,112,962 [Letsmger et al. (Letsmger)], the contents of which are hereby incorporated by reference Letsmger teaches a linker arm for solid support synthesis of oligonucleotides and oligonucleotide deπvatives have the following formula Thus Letsmger teaches an oxalyl linker arm which purportedly release the synthesized oligonucleotide or oligonucleotide deπvate in a peπod of 1-30 minutes in a manner that leaves the oligonucleotide fully protected The oxalyl linker arm purportedly can be rapidly cleaved by 5% ammonium hydroxide m methanol, ammonium hydroxide, wet tertiary amine, tπethylamine/alcohol, tπethylamme/methanol, tπethylamine/ethanol, aqueous tπmethylamme and other bases Unfortunately, the oxalyl linker arm of Letsmger suffers fiom its purported advantage Specifically, the present inventors have discovered that the oxalvl linker arm of Letsmger is susceptible to significant spontaneous hydrolysis (e g spontaneous hydrolysis of ~ 10-40° o per month) which renders it difficult to use in commercial operations The oxalvl arm is also difficult to prepare because it requires using oxalyl chloπde, which is highly reactive, toxic and therefore dangerous Regardless of the specific nature of the linker arm, it is generally accepted in the art that the linker arm is not reusable after production and cleavage of the desired oligonucleotide Thus, conventional linker arms may be regarded as non- recyclable This is illustrated in Figure 1 which illustrates the conventional use of a succinyl linker arm for the production of an oligonucleotide Thus, as illustrated, after cleavage of the desired oligonucleotide, the support is irreversibly linked to the linker compound (I e . the succinyl moiety) and cannot be reused The art is in need of a linker arm for solid support oligonucleotide synthesis, which linker arm is recyclable. More specifically, the art is in need of a linker arm capable of repeated oligonucleotide synthesis/cleavage. In published International patent application WO 97/23496 [Pon et al.], the contents of which are hereby incorporated by reference, there is reported the first recyclable linker arm. This linker arm is based on a derivatized solid support having the following formula: wherein: R 8 is selected from the group consisting of a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 - C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group; X 3 and X 4 are the same or different and are selected from the group consisting of -0-, -S-, -S(O) 2 - and -N(R 12 )-; R 12 is selected from the group consisting of a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group; and Y is selected from the group consisting of: -CH-,-CH->-; -CH 2 s -CH 2 -0-CH 2 -; -CH->-CH 2 -CH 2 -; -CH=CH-; -CH=C(CH 3 )-; -C(CH 3 )=C(CH 3 )-; -CH 2 -C(=CH 2 )-; and -CH-rS-CH-,- . While a linker arm based on the solid support described by Pon et al. is a significant advance in the art, there is still room for improvement. Specifically, the solid support described by Pon et al. has the following disadvantages. First, pπor to attachment of the linker moiety, the solid support must be deπvatized by a process composing the step of reacting together the compounds of Formulae I, II and III HO-R— - X , H HX' — [SUPPORT] (!) (ii) (in) wherein R 8 , X\ X 4 and Y are as defined above Practically, this involves two steps - 1 e , reaction of the compound of Formula III with one of the compounds of Formulae I and II and subsequent reaction with the other of compounds of Formulae I and II Thus, the disadvantage is additional labour required to effect a two-step deπvatization of the solid support Second, each step of the deπvatization described m the previous paragraph has the potential of incompletely deπvatizing each HX 4 - moiety on the support thereby increasing the likelihood of a heterogeneous surface Practically, it becomes necessary to block or cap undeπvatized HX 4 - moieties so that the linker moiety does interact with them Thus, the disadvantage is additional labour and cost required to effect deπvatization of the solid support Third, a linker arm based on the deπvatized support descπbed by Pon et al is not as resistant to partial cleavage duπng regeneration as a deπvatized suppoπ having a more fully saturated moiety In light of these disadvantages, it would be desirable to have an improved recyclable solid state support mateπal useful in the oligonucleotide synthesis It would be especially desirable if the the linker moiety could be attached to the support mateπal with little or no deπvatization required of the latter DISCLOSURE OF THE INVENTION It is an object of the present invention to provide a novel solid support for ohgonculeotide synthesis which obviates or mitigates at least one of the above- mentioned disadvantages of the pπor art It is another object of the present invention to provide a novel process for producing the solid support. It is an object of the present invention provide a novel linker arm for solid support oligonucleotide synthesis which obviates or mitigates at least one of the above-mentioned disadvantages of the prior art. It is another object of the present invention to provide a novel process for producing a linker arm for solid support oligonucleotide synthesis. Accordingly, in one of its aspects, the present invention provides a reusable linker arm for solid support oligonucleotide synthesis, the linker arm comprising the following formula: Z— O— T [SUPPORT] wherein Z is a linker moiety and T is an organic radical. In another of its aspects, the present invention provides a reusable linker arm for solid support oligonucleotide synthesis, the linker arm comprising the following formula: NUCLEOSIDE— Z— O— T [SUPPORT] wherein Z is a linker moiety and T is an organic radical. In yet another of its aspects, the present invention provides a process for production of a reusable linker arm for oligonucleotide synthesis having the following formula: Z— O— T [SUPPORT] wherein Z is a linker moiety and T is an organic radical, the process comprising the step of reacting together the compounds of Formulae I and II: Z — OH HO-T — [SUPPORT] (I) (II) wherein Z and T are as defined above. In another of its aspects, the present invention provides a process for production of a reusable linker arm for oligonucleotide synthesis having the following formula: NUCLEOSIDE— Z— O— T [SUPPORT] wherein Z is a linker moiety and T is an organic radical, the process comprising the step of reacting together the compound of Formulae I. II and III: HO- Z— OH HO- T— [SUPPORT] (I) (II) NUCLEOSIDE- OH wherein Z and T are as defined above. In yet another of its aspects, the present invention provides a process for producing an oligonucleotide having a desired sequence comprising the steps of: (i) reacting a linker arm having the formula: NUCLEOSIDE— Z—O—T [SUPPORT] wherein Z is a linker moiety and T is an organic radical, with at least one oligonucleoside base until an oligonucleotide having the desired sequence is produce; (ii) cleaving the oligonucleotide having the desired sequence to produce a free oligonucleotide have the desired sequence; and a used linker arm; and (iii) recycling the used linker arm to Step (i). As used throughout this specification, the term "oligonucleotide" is intended to have a broad meaning and encompasses conventional oligonucleotides, backbone-modified oligonucleotides (e.g. phosphorothioate, phosphorodithioate and methyl-phophonate analogs useful as oligotherapeutic agents) and oligonucleotide derivatives such as oligonucleotide-peptide conjugates. Throughout this specification, when reference is made to a substituted moiety, the nature of the subsitution is not specification restricted and may be selected from the group consisting of a C,-C 20 alkyl groups, aC 5 -C 30 aryl group a C 5 -C 40 alkaryl group. BRIEF DESCRIPTION OF THE DRAWINGS Embodiments of the present invention will be described with reference to the accompany drawing in which: Figure 1 illustrates a specific process pathway for conventional oligonucleotide synthesis; and Figures 2 and 3 illustrate specific preferred embodiments of the present invention. BEST MODE FOR CARRYING OUT THE INVENTION Initially, to facilitate an understanding of the invention, reference will be made to Figure 1, which illustrates a conventional process for solid support oligonucleotide synthesis Thus, the initial step of the process illustrated m Figure 1 compπses reacting a linking compound, such as succmic acid (while succmic acid is illustrated, succmic anhydπde may also be used), with a conventional amme- termmated support The reaction results in the formation of an amide linkage between the linking compound and the support to produce succmyl-support conjugate Next, the succmyl-support conjugate is reacted with a desired initial nucleoside to produce a linker arm In the illustrated nucleoside, DMT is dimethyoxytπtyl, B is the nucleobase and R' is H (for deoxyπbonucleosides) or OR (for πbonucleosides) wherein R is H or a conventional blocking/ protecting group The reaction results in the formation of an ester linkage between the linking compound and the desired initial nucleoside at the 3' position of the latter The linker arm is then used m conventional oligonucleotide synthesis (e g in a conventional automated synthesizer) to produce an oligonucleotide of desired sequence attached to the linker arm The oligonucleotide is then cleaved from the linker by hydrolysis This serves to cleave the ester bond thereby freeing the oligonucleotide and an amine- termmated, non-reusable linker arm The present inventors have surpπsingly and unexpectedly discovered that a support having a hydroxy-termmated functionality may be combined with a conventional linking compound to produce linker arm which may used to synthesize an oligonucleotide of desired sequence A key feature of the mvetion is that the linker arm may be regenerated or recycled after cleavage of the oligonucleotide of desired sequence To the inventors' knowledge, this is the first discovery of a deπvatized support which may be used repeatedly m oligonucleotide synthesis The reusable linker arm of the present invention has the following formula- Z— 0— T [SUPPORT] wherein Z is a linker moiety and T is an organic radical. Preferably, T contains at least one carbon. Preferably, T is a C,-C 300 organic moiety, more preferably a C,-C 200 organic moiety, most preferably a C C^ organic moiety. As will be appreciated by those of skill in the art, T may be a saturated or unsaturated organic moiety. Further, T may contain one or more heteroatoms. For example, T may comprise at least one heteroatom selected from N and O. In one prefeπed embodiment, the organic moiety in T comprises at least one moiety having the formula: O II ■ C - In another prefeπed embodiment, the organic moiety in T comprises at least one moiety having the formula: N(H) In yet another preferred embodiment, the organic moiety in T comprises at least one moiety having the formula: ■i l¬ O II — N(H)C- In yet another preferred embodiment, the organic moiety m T compπses at least one moiety having the formula - C - O - C - In yet another preferred embodiment, the organic moiety in T compπses at least one moiety having the formula O II -C-O- Further, those of skill in the art will recognize that the organic moiety m T may be unsubstituted or substituted For examples, the organic moiety of T may be substituted by at least one moiety selected from the group compπsmg a C ] -C 40 alkyl group, a C 5 -C 40 aryl group, a C,-C 40 alkoxy group, a C,-C 40 ester group, a C,-C 40 hydroxy group, a C 2 -C 40 acrylate group and a C,-C 40 alkylaryl group In one preferred embodiment, T has the formula ~ E CH 23 — E° - CH 2 — CH 2 — θ3— CH 2 ^- wherein q and s are the same or different and each is an integer having a value of 0-40 and r is an integer having a value of 1 -200. In this embodiment, it is further preferred that q and s are the same or different and each is an integer having a value of 1-20 and r is an integer having a value of 1-150. In another prefeπed embodiment, T has the formula: wherein a is 0 or 1, Q is an organic moiety, R 8 is hydrogen or a protecting group and b is an integer having a value of 0-40. In this embodiment, a may be 0 and R 8 may be hydrogen. Further, a may be 1 and R 8 may be a protecting group. Non-limiting examples of protecting groups may be selected from the group comprising acetyl, chloroacetyl, methoxyacetyl, t-butyl phenoxyacetyl, phenoxyacetyl, trityl, methoxytrityl, dimethoxytrityl (DMT), dialkylphosphite, pivalyl-isobutyloxycarbonyl, f-butyldimethylsilyl, phenoxyacetal, 9- phenylxanthen-9-yl (pixyl), tetrahydropyranyl, methoxytetrahydropyranyl, methoxymethyl, benzyloxymethyl, methoxyethoxymethyl, methylthiomethyl, dialkylphosphate, levulinyl, dimethylphenylsilyl, trimethylsilyl, isopropyl- dimethylsilyl, diisopropylmethylsilyl, diethylisopropylsilyl, triisopropylsilyl, acetyl, benzoyl, pivaloyl, trifluoroacetyl, allyl, benzyl, o-nitrobenzyl, o- hydroxystyryldimethylsilyl, 2-oxo- 1 ,2-diphenylethyl, allyloxycarbonyl, monomethoxymethyl, nitroveratryloxycarbonyl, dimethoxybenzoin, dimethoxybenzoin carbonate, methylnitropiperonyl carbonate, fluorenyl- methoxycarbonyl, 2-phenylsulfonylethoxycarbony, fluorophenyl- methoxypiperidinyl and mixtures thereof. In this embodiment, Q may be a moiety having the formula: - io- wherein q, r, s, t and u are the same or different and each is an integer having a value of 0-40 and R a is selected from the group comprising hydrogen, hydroxyl, a C,-C 40 alkyl group, a C 5 -C 40 aryl group, a C 1 -C 40 alkoxy group, a C,-C 40 ester group, a C,-C 40 hydroxy group, a C 2 -C 40 acrylate group and a C 5 -C 40 alkylaryl group. Preferably, s is 0, q, r and u are the same or different and each is an integer having a value of 1-10, t is an integer of 1-5 and R is hydroxyl. In yet another prefeπed embodiment, T has the formula: OR 8 — O -f Q 3" CH - CH 2 — O -£CH 2 3τ— " wherein a is 0 or 1, Q is an organic moiety, R 8 is selected from the group comprising hydrogen, hydroxyl, a C,-C 40 alkyl group, a C 5 -C 40 aryl group, a C,- C 40 alkoxy group, a C [ -C 40 ester group,a C,-C 40 hydroxy group, a C 2 -C 40 acrylate group and a C 5 -C 40 alkylaryl group, and b is an integer having a value of 0-40. Preferably, Q is a C,-C 100 organic moiety. As will be appreciated by those of skill in the art, Q may be a saturated organic moiety or an unsaturated organic moiety. It is preferreed that Q is a C,-C 100 organic moiety comprising at least one heteroatom selected from N and O. In one prefeπed embodiment, the organic moiety Q comprises at least one moiety having the formula: O II -C- In another prefeπed embodiment, the organic moiety Q comprises at least one moiety having the formula: - N(H) - . In yet another embodiment, the organic moiety Q compπses at least one moiety having the formula: o II — N(H)C- In yet another embodiment, the organic moiety Q compπses at least one moiety having the formula: - C - O - C - . In yet another embodiment, the organic moiety compπses at least one moiety having the formula: O II -C-O- As will be appreciated by those of skill in art, the organic moiety Q may unsubstituted or substituted. For example, the organic moiety Q may be substituted by at least one moiety selected from the group comprising a C,-C 40 alkyl group, a C 5 -C 40 aryl group, a C,-C 40 alkoxy group, a Cι-C 40 ester group, a C,- C 40 hydroxy group, a C 2 -C 40 acrylate group and a C 5 -C 40 alkylaryl group. In one prefeπed embodiment, Q has the formula: wherein each of x, y and z is an integer having a value of 1-40. In the above formula for the present linker arm, Z is a linker moiety. As will be discussed below, Z is derived from a linker compound have the general formula HO-Z-OH (Formula I below). The nature of the linker compound is not particularly restricted. In one prefeπed embodiment, linker moiety Z has the formula: O O II II HO— C— CH->— CH>— C- As will be apparent to those of skill in the art, this linker moiety may be derived from succinic acid or succinic anhydride. In another prefeπed embodiment, linker moiety Z has the following formula: As will be apparent to those of skill in the art, this linker moiety may be derived from diglycolic acid or diglycolic anhydride. In yet another prefeπed embodiment, linker moiety Z has the following formula: 0 O II II HO-C— C — As will be apparent to those of skill in the art, this linker moiety may be derived from oxalic acid or oxalyl chloride. In yet another, and most, prefeπed embodiment, linker moiety Z has the following formula: wherein: R 1 , R 2 and R 3 are the same or different and are selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group; R 4 and R 5 are the same or different and are selected from the group consisting of hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group; X 1 is selected from the group consisting of -O-, -C(O)-, -S-, -S(O) 2 - and -N(R)-; R is selected hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group; n is 0, 1 or 2; and one of A 1 and B 1 is selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C r C 20 alkyl group, a substituted or unsubstituted C 5 - C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, and the other of A 1 and B 1 has the formula: wherein p is 0 or 1 , X 2 is selected from the group consisting of -O-, -S-, -C(O)-, -S(O) 2 - and -N(R)-, R is selected from the group comprising hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 - C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, R 6 and R 7 are the same or different and are selected from the group consisting of hydrogen, a substituted or unsubstituted Cι-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, and m is 0, 1 or 2. In this embodiment, B 1 preferably is selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group. Preferably, at least one, more preferably each, of R, R 4 , R\ R 6 and R 7 is hydrogen and preferably at least, more preferably both, of m and n are 1. It is further preferred that each of R 1 , R 2 and R 3 is hydrogen and that X 1 and X 2 are both -O-. Thus, in this embodiment, the most prefeπed form of linker moiety Z is derived from hydroquinone-O,O'-diacetic acid. In yet another prefeπed embodiment, linker moiety Z has the following formula: wherein R 4 . R\ R b and R' are the same or different and are selected from the group consisting of hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, Y is selected from the group consisting of O, S, SO 2 and O-((CH 2 ),-O) q , 1 is an integer less than or equal to 60, q is an integer in the range of 1 - 1000, n and m are the same or different and are 1 or 2, with the proviso that, when Y is O, at least one of n and m is 2. Preferably, 1 is an integer in the range of 1 - 10, and q is an integer in the range of 1 - 1000. In this embodiment, the most prefeπed form of linker moiety Z is derived from thiodiglycolic acid (i.e. R 4 =R 3 = R 6 =R 7 =H. n=m=l and Y=S). The SUPPORT in the above formula is a conventional solid support. The nature of the solid support is not particularly restricted and is within the purview of a person skilled in the art. Thus, the solid support may be an inorganic substance. Non-limiting examples of suitable inorganic substances may be selected from the group consisting of silica, porous glass, aluminosilicates, borosilicates, metal oxides (e.g. aluminum oxide, iron oxide, nickel oxide) and clay containing one or more of these. Alternatively, the solid support may be an organic substance such as a cross-linked polymer. Non-limiting examples of a suitable cross-linked polymer may be selected from the group consisting of polyamide, polyether, polystyrene and mixtures thereof The prefeπed solid support for use herein is conventional and may be selected from controlled pore glass bead or polystyrene beads. Further, the support may be either in particle form (e.g., beads), three-dimensional slabs (e.g., polymeric inserts and foams) or in a flat two-dimensional like format (e.g., plastic sheets, glass chips, silicon wafers, etc.). The material used for the support may also be soluble in certain solvents (e.g., liquid-phase supports), but can be precipitated or crystallized from other solvents. The reusable linker of formula: Z— O— T [SUPPORT] (again, Z is a linker moiety and T is an organic radical), may then be reacted with a conventional nucleoside-linker compound to produce another linker arm according to the present invention. This other linker arm has the following formula: NUCLEOSIDE— Z—O—T — -[SUPPORT] wherein Z is a linker moiety and T is an organic radical. The discussion herein above with respect to Z and T applies equally here. Preferably, in the above formula, NUCLEOSIDE is a moiety selected from one of the following formulae: wherein R 6 and R 10 are the same or different and are hydrogen or a protecting group, R is hydrogen (for deoxyπbonucleosides or DNA) or -OR 11 (for πbonucleosides or RNA) wherein R 11 is hydrogen or a protecting group, and B * a nucleic acid base Thus, m the case of RNA, there are two hydroxyl groups which may be protected Also, the linker can be attached to either the 5'-, 3'- or (if ribose) 2'- hvdroxyl positions Indeed, for RNA sequences, it makes little difference whether the ester linker formed between the nucleoside and the linker compound is at the 2'- or 3'- hydroxyl position of the nucleoside Thus, those of skill m the art will recognize that the nucleoside may be protected or blocked at the vaπous of its hydroxyl moieties Non- mitmg examples of useful protecting groups may be selected from the group consisting of acetyl, chloioacetyl, methoxyacetyl, t-butyl phenoxyacetyl, phenoxyacetyl, tπtyl, methoxytπtyl, dimethoxytπtyl (DMT), dialkylphosphite, pivalyl-isobutyloxvcarbonyl, r-butyldimethvlsilyl, phenoxyacetal, 9-phenylxanthen-9-yl (pixyl), tetrahydropyranyl, methoxvtetrahydropyranyl, methoxymethyl, benzyloxymethyl, methoxyethoxymethyl, methylthiomethyl, dialkylphosphate, levulmyl, dimethylphenylsilyl, tπmethylsilyl, isopropyldimethylsilyl, diisopropylmethylsilyl, diethylisopropylsilyl, triisopropylsilyl, acetyl, benzoyl, pivaloyl, trifluoroacetyl, allyl, benzyl, o-nitrobenzyl, o- hydroxystyryldimethylsilyl, 2-oxo- 1 ,2-diphenylethyl, allyloxycarbonyl, monomethoxymethyl, nitroveratryloxycarbonyl, dimethoxybenzoin, dimethoxybenzoin carbonate, methylnitropiperonyl carbonate, fiuorenyl- methoxycarbonyl. 2-phenylsulfonylethoxycarbony, fluorophenyl- methoxypiperidinyl and the like. As is known in the art, the main prerequisite for the protecting group used on the 5'-hydroxyl position is its ability to be selectively removed without causing cleavage of the linker arm. Thus, the prefeπed protecting group for desired 5'-hydroxyl position(s) is the acid labile dimethoxytrityl group. The main prerequisite for protecting groups on other hydroxyl positions, is stability to the conditions used for removal of the above protecting group. These latter protecting groups may be removed by the same conditions used to cleave the linker (discussed below) or separate conditions. The prefeπed protecting groups for these positions are trialkylsilyl (i.e. t-butyldimethylsilyl) or acetyl. Additional information may be obtained from the following references: 1. T. W. Greene and P. G. M. Nuts, "Protecting Groups in Organic Synthesis", Second Edition (1991 ). John Wiley and Sons, Inc., NY; 2. M. Schelhaas and H. Waldman, "Protecting Group Strategies in Organic Synthesis", Angew. Chemie Int. Ed. Engl. 35, 2056-2083 (1996); 3. M. J. Gait, ed., "Oligonucleotide Synthesis A Practical Approach", IRL Press, Oxford (1984); 4. S. A. Narang, ed., "Synthesis and Applications of DNA and RNA", Academic Press, Inc., Orlando (1987); and 5. S. Agrawal, ed., "Methods in Molecular Biology, Vol.20: Protocols for Oligonucleotides and Analogs", Humana Press, Totowa, NJ ( 1993); the contents of each of which are hereby incorporated by reference, for a discussion of other possible hydroxyl protecting groups. The manner by which the desired nucleoside may be protected is conventional and withm the purview of a person skilled in the art See, for example United States patent 3,400,190 (Melby), United States patent 4,458,066 (Caruthers et al.), the contents of each of which are hereby incorporated by reference A prefeπed method for production of deoxyπbonucleosides in the context of the present invention is to use a nucleoside with a 5'-dιmethoxytntyl protecting group and an appropnate exocychc amino protecting group, e g , N 6 -benzoyl-5'- dιmethoxytπtyl-2'-deoxyadenosιne, N 4 -benzoyl-5'-dιmethoxytπtyl-2'- deoxycytidme, 5'-dιmethoxytntyl-N 2 -ιsobutyryl-2'-deoxyguanosme, or 5'- dimethoxytπtylthymidine A prefeπed method for production of πbonucleosides in the context of the present invention is to use a 5'-dιmethoxytπtyl protected nucleoside, with appropnate exocychc ammo protection, and no protecting groups on either of the 2'- or 3'- hydroxyl positions The linker can then react with either one of the two adjacent hydroxyl groups (it doesn't matter which) to give a mixture of 2'- and 3'- hnkages The unreacted hydroxyl groups may then be acetylated by treatment of the immobilized nucleoside with acetic anhydπde Alternatively, πbonucleosides which have a 5'-dιmethoxytπtyl group, appropnate exocychc amino group protection, and either a 3'-hydroxyl protecting group or a mixture of 2'- and 3'- protecting groups can be used The 3'-protected compounds are generally unwanted isomers which are simultaneously produced when the 2'-hydroxyl position is protected and having little other use The reusable linker arm having the formula Z— O— T [SUPPORT] may be produced by a process comprising the step of reacting together the compound of Formulae I and II: Z— OH HO- T — [SUPPORT] (I) (II) wherein Z and T are as defined above. The reusable linker arm having the formula: NUCLEOSIDE— Z—O—T [SUPPORT] comprises the step of reacting together the compounds of Formulae I, II and III: HO- Z-OH HO- T — [SUPPORT] (I) (H) NUCLEOSIDE- OH (in) wherein Z and T are as defined above. The compounds of Formulae I and II or of Formulae I, II and III (depending on which version of the present linker arm is being produced) are preferably reacted in the presence of an activating agent. As used throughout this specification, the term "activating group" is intended to have a broad meaning and is intended to encompass electrophilic reagents capable of activating a carboxyl moiety (e.g., on the linking compound of Formula II) by attachment of a leaving group to the acyl carbon of the carboxl moiety - see, for example, M. Bodanszky, "Principles of Peptide Synthesis", Second Edition, Springer- Verlag, Berlin (1993), the contents of which are hereby incorporated by reference. Thus, the activating agent should be capable of initiating at least one of the following: (a) formation of a reactive acylating agent (this is an example of a derivate) from the carboxyl moeiy in a separate step or steps, followed by immediate treatment with the amino component (in this case, for example, an amino-terminated support) to form an amide linkage or a hydroxy component (in this case a hydroxy-terminated support or a hydroxyl group on the desired nucleoside) to form an ester linkage; (b) formation of an isolable acylating agent, separately, optionally with purification prior to treatment with the amino or hydroxy component as discussed in (a); and (c) formation of an acylating intermediate in the presence of the amino/ hydroxy component, by the addition of an activating agent to a mixture of the two components. Thus, each of (a), (b) and (c) are applicable to the formation of both carboxylic esters and amides and all three routes can be used to attach nucleosides to supports. For example, the Letsinger method, which first reacts oxalyl chloride with triazole, and then adds a nucleoside to the resulting oxalyl triazolide is an example of route (a). Conversion of the carboxylic acid group into an "active" ester using either p-nitrophenol, or di-, tri-, tetra-, or penta- chlorinated or fluorinated phenols, or N-hydrosuccinimide are common examples of route (b). Route (c) has been the most commonly used method in recent years and both the carbodiimide reagents (dicyclohexylcarbodiimide, l-(3-dimethylaminopropyl)- ethylcarbodiimide, and diisopropylcarbodiimide) and uronium reagents (O-(7- azabenzotriazol- 1 -yl)- 1.1,3 ,3-tetramethyluronium hexafluorophosphate (HATU), 2-(lH-benzotriazol-l-yl)-l ,l,3,3-tetramethyluronium hexafluorophosphate, (HBTU)) may be used in this approach. In a prefeπed embodiment, in addition to an activating reagent, the reaction of the compounds of Formulae I, II and III is conducted in the presence of a nucleophilic catalyst or additive (typically 4-dimethylamino pyridine (DMAP), 1-hydroxybenzotriazole (HOBt), or l-hydroxy-7-azabenzotriazole (HOAt)) to speed up the reaction and a tertiary amme base (typically tnethylamme, pyπdine, or dusopropylethylamme) to ionize the carboxylic acid group Thus, those of skill in the art will recognize that the precise nature of the activation agent is not particularly restncted provided, of course, that the activated carboxylic acid group is capable of initiating formation of the ester or amide linkage, as appropriate, and the activating reagent does not have any deleteπous effect on the desired nucleoside Thus, activation of the carboxylic acid by conversion into an acid chloπde, an active ester (I e , nitrophenyl, mtrophenylthio, tnchlorophenyl, tπfluorophenvl, pentachlorophenyl, pentafluorophenyl, or 3-hydroxv-2,3- dιhydro-4-oxo-benzotπazme esters), an active hydroxylamine ester (1 e , N- hydroxyphthahmide or N-hydroxysuccimmide), acid anhydride, or mixed anhydπde will produce deπvates which will form the desired linkage, and thus, these strategies are encompassed herein Non-limiting examples of actuating agents may be selected from the group consisting of arylsulfonyl chloπdes (e g , benzenesulfonyl chloπde (BS- Cl), mesitvlenesulfonyl chloπde (MS-C1), tπisopropylsulfonylchloπde (TPS-C1)), active arylsulfonyl esters (I e , lmidazole, tnazole, nitrotπazole, or tetrazole esters ofBS-Cl. MS-ClorTPS-Cl), 2-ethoxy-l-(ethoxycarbonyl)-l,2-dιhydroquιnolme (EEDQ), acyl carbonates, l,r-(carbonyldιoxy)dιbenzotπazoles, chlorotπmethyl- silane, carbodnmides (l e , dicyclohexylcarbodnmide (DCC), l-(3- dιmethylammopropyl)-ethylcarbodιιmιde (DEC), dnsopropylcarbodiimide (DIC)) either alone or in combination with auxiliary nucleophiles (l e , 1 - hydroxybenzotπazole (HOBt), l-hydroxy-7-azabenzotπazole (HO At), N- hydroxysuccmimide (HOSu), or 3-hydroxy-3 ,4-dιhydro- 1 ,2,3-benzotnazm-4-one (HOObt)) and/or catalysts (l e , 4-dιmethylammopyndιne (DMAP) or N- methyhrmdazole (NMI)), or uronium salts (l e , tetramethyluronium chloπde (TMU-C1), 2 -( l H-benzotπazol- 1 -yl)- 1 , 1 , 3 , 3 -tetramethyluronium hexafluorophosphate (HBTU), 2-( l H-benzotπazol- l -yl)- l , 1 ,3 ,3- tetramethyluronium tetrafluoroborate (TBTU), 2-succmιmιdo-l ,l,3,3- tetramethyluromum tetrafluoroborate (TSTU), 2-(3,4-dιhydro-4-oxo-l,2,3- benzotriazin-3-yl)-l, 1,3, 3 -tetramethyluronium tetrafluoroborate (TDBTU), 2-(2- oxo-l(2H)-pyridyl-l,l,3,3-tetramethyluronium tetrafluoroborate (TPTU), 2-(5- norbornene-2,3-dicarboximido)-l,l,3,3-tetramethyluronium tetrafluoroborate (TNTU), O-(7-azabenzotriazol- 1 -yl)- 1 ,3-dimethyl- 1 ,3 -dimethyleneuronium hexa- fluorophosphate (HAMDU), 0-(7-azabenzotriazol-l-yl)-l,3-dimethyl-l,3-tri- methyleneuronium hexafluorophosphate (HAMTU), O-(7-azabenzotriazol-l-yl)- l,l,3,3-bis(pentamethylene)uronium hexafluorophosphate (HAPipU), O-(7- azabenzotriazol- 1 -yl)- 1,1,3 ,3 -bis(tetramethylene)uronium hexafluorophosphate (HAPyU), O-( 7 -azabenzotriazol- 1-yl)- 1 , 1 , 3, 3 -tetramethyluronium hexafluorophosphate (HATU)) either alone or in combination with auxiliary nucleophiles (i.e., 1 -hydroxybenzotriazole (HOBt), 1 -hydroxy-7-azabenzotriazole (HOAt), N-hydroxysuccinimide (HOSu), or 3-hydroxy-3,4-dihydro- 1,2,3- benzotriazin-4-one (HOObt)) and or catalysts (e.g. 4-dimethylaminopyridine (DMAP) or N-methylimidazole (NMI)) orphosphonium salts (e.g. benzotriazol- l-yl-oxytris(dimethylamino)phosphonium hexafluorophosphate (BOP), benzotriazole- 1 -yl-oxy-trispyrrolidinophosphonium hexafluorophosphate (PyBOP), 2-(benzotriazol- l -yl)oxy- l ,3-dimethylimidazolidinium hexafluorophosphate (BOI), bromo tris(pyrrolidino)phosphonium hexafluorophosphate (PyBroP), 7-azabenzotriazol- l -yloxytris- (dimethylamino)phosphonium hexafluorophosphate (AOP), and 7- azabenzotriazol-l -yloxytris(pyπolidino)phosphonium hexafluorophosphate (PyAOP)) either alone or in combination with auxiliary nucleophiles and/or catalysts (discussed above) will also produce the desired linkage. Other examples of suitable activating reagents may be found in any of the following references: M. Bodanszky, "Principles of Peptide Synthesis", Second Edition, Springer- Verlag, Berlin (1993); J. Jones, "Amino Acid and Peptide Synthesis", Oxford University Press, Oxford (1992); G Grant, "Synthetic Peptides: A Users Guide", W. H. Freeman & Co., NY (1992); E Haslam, Tetrahedron, 36, pg 2409, (1980), and M A Og aruso and J F Wolfe, "Synthesis of Carboxylic Acids, Esters and Their Denvatives", John Wiley & Sons, Chicester (1991), the contents of each of which are hereby incorporated by reference In producing the present linker arm, the order of reaction is not particularly restπcted Thus, in one embodiment (this is the prefeπed embodiment), the compounds of Formulae I and III are initially reacted to form a conjugate which is reacted with the compound of Formula II In another embodiment, the compounds of Formulae I and II are initially reacted to form a conjugate which is reacted with the compound of Formula III The addition of compounds of Formulae I and III to Formula II, usually will not result in the quantitative conversion of each immobilized hydroxyl group into a deπvatized gand Therefore, it is prefeπed that unreacted hydroxyl groups on the surface of the support be protected (capped) by reaction with a capping reagent This will mitigate the free hydroxyl group participating in subsequent oligonucleotide chain extension reactions, resulting in defect sequences lacking the terminal nucleoside Preferably, the capping reagent should be reversible so that the capping agent can be removed to regenerate the hydroxyl sites pπor to the next round of support deπvatization Capping of the unreacted sites is conventional and can be performed by reaction with an activated carboxylic acid or anhydπde to form an ester, or by addition of a protecting group, as descπbed hereinabove Thus, for example, t-butylphenoxyacetic anhydπde, methoxyacetic anhydπde or preferably chloroacetic anhydπde, combined with 2,6-lutιdιne and N-methyhmidazole in THF solution are useful examples of capping reagents With reference to Figure 2 there is illustrated a prefeπed pathway illustrating the use of the present linker arm m a recycled/regenerated manner In Figure 2, DMT refers to dimethoxytπtyl and B refers to a nucleobase as descπbed hereinabove As will be apparent to those of skill m the art, the support is recycled after oligonucleotide cleavage and support regeneration to a point in the reaction scheme where it may again be coupled with the HQPD-nucleoside conjugate for further oligonucleotide synthesis. With further reference to "Oligo Synthesis" (Step #3) in Figure 2, once the present linker arm has been produced, it may be used in the conventional manner to synthesize an oligonucleotide - see, for example, United States patent 5,112,962 (Letsinger), incorporated by reference hereinabove. Once the oligonucleotide has been synthesized, it may be cleaved from the solid support to yield the free oligonucleotide and the support may then be regenerated - see Step #4 of Figure 2. The cleavage step comprises hydrolysis at the point of attachment of the initial nucleoside to the linking compound. The regeneration of the support involves the removal of two moieties: (i) the removal of the structure represented by Formula I (above) from Formula II (above), which occurs simultaneously with the release of the oligonucleotide product, and (ii) the removal of the moiety used to protect (cap) unreacted hydroxyl sites of Formula II (above) on the support. Removal of these two moieties can occur simultaneously or separately to regenerate the support. Simultaneous removal of both moieties using only a single reagent is simpler but care should be taken to use reagents which will not deleteriously affect the oligonucleotide product. A two-step regeneration involving the removal of the oligonucleotide using one reagent (typically ammonium hydroxide) and then treatment of the support with a second reagent (which may be faster but otherwise damaging to the oligonucleotide product thereby necessitating use of a two-step regeneration) allows flexibility in the choice of capping and regeneration reagents. The reagent used to effect cleavage is not particularly restricted and is within the purview of a person skilled in the art. Preferably, the reagent is a base mild enough not to damage the oligonucleotide product but sufficiently strong to effect rapid cleavage. Non-limiting examples of suitable reagents for this purpose may be selected from the group consisting of ammonium hydroxide, ammonium hydroxide/methanol, ammonia/methanol, ammonium hydroxide/methylamine, potassium carbonate/methanol, t-butylamine, ethylenediamine, mefhylamine, dimethylamine, trimethylamine/water and the like. Cleavage may also be performed under neutral conditions using fluoride ion (i.e. 1M tetrabutylammonium fluoride/THF or triethylamine trihydro fluoride). The reagent used to remove the capping reagent from unreacted sites may consist of the above reagents or other stronger bases such as sodium or potassium hydroxide. In our prefeπed embodiment, ammonium hydroxide can be used to cleave the oligonucleotide product from the support, remove the HQPD linker arm, and cleave chloroacetyl protected hydroxyl groups in a single regeneration step. The prefeπed temperature for the cleavage and regeneration is room temperature, but higher or lower temperatures can be employed, subject to the limitations of the apparatus used. With reference to Figure 3, there are illustrated specific prefeπed examples of hydroxyl reusuable linker arms falling within the scope of the present invention. Embodiments of the invention will be illustrated in the following Examples which should not be construed as limiting the scope of the invention. In the Examples, the following materials were used: 1. Long chain alkylamine (LCAA) or glycerol (Gly) derivatized controlled pore glass (CPG) beads (120/200 mesh) were obtained from CPG Inc (Lincoln Park, NJ); 2. Toyopearl AF-amino-650M and HW65F supports were obtained from TosoHaas (Montgomeryville, PA); 3. Other supports were obtained from the manufacturers listed in Tables 1 and 2; 4. HQPD, Hydroquinone-O,O'-diacetic acid, commercially available from Lancaster Synthesis Ltd. (Lancashire, England); 5. Ammonium hydroxide solutions (28-30%) and solvents were obtained from VWR Canlab (Edmonton, Alberta, Canada); 6. Capping solutions were formulated as either Cap A (acetic anhydride/2, 6-lutidine/THF in a volume ratio of 1:1:8) and Cap B (N-methylimidazole and THF in a volume ratio of 16:84) or Cap A (chloroacetic anhydride and THF, 17% by weight) and Cap B (2, 6-lutidine and N-methylimidazole in THF in a volume ratio of 12:16:72); 7. Anhydrous pyridine and acetonitrile, distilled from CaH 2 ; 8. DIEA, diisopropylethylamine, reagent grade; 9. MeCN, acetonitrile, low water DNA synthesis grade; 10. DMAP, 4-dimethylaminopyridine, reagent grade; 11. DEC, l-(3-dimethylaminopropyl)-ethylcarbodiimide, reagent grade; 12. Sulfurizing reagent, Beaucage thiolating reagent, from Pharmacia Biotech, was used as a 0.05M solution in acetonitrile; and 13. HBTU, 2-(lH-benzotriazol-l-yl)-l,l,3,3-tetramethyluronium hexafluoro-phosphate, reagent grade; In the following Examples the amount of nucleoside (loading) on the insoluble supports was determined by spectrophotometric trityl analysis. In this procedure, a sample of support (4-5 mg) was accurately weighed directly into a 10 mL volumetric flask. A solution of dichloroacetic acid in 1 ,2-dichloroethane in a volume ration of 5:95 was then added to fill the flask. The contents were then thoroughly mixed and the absorbance of the orange coloured solution was measured at 503 nm using a Philips UV/Vis spectrophotometer. The nucleoside loading (in μmol/g of CPG) was then calculated as: Loading = (A 503 x Vol x 1000) / (Wt x 76) wherein A 503 = absorbance at 503 nm, Vol = solution volume in mL, and Wt = amount of CPG tested in mg. The accuracy of the trityl determination was approximately ± 2-3%. Example 1 - SYNTHESIS OF NUCLEOSIDE-3'-0-HODA HEMIESTERS 5'-Dimethoxytrityl-N-protected deoxyribonucleoside (10 mmol), hydroquinone-O, O'-diacetic acid (15 mmol, 3.39 g), 4-dimethylaminopyridine ( 1 mmol, 122 mg), and l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride ( 15 mmol, 2.88 g) were combined in a 100 mL round bottom flask equipped with a magnetic stir bar. Triethylamine (0.8 mL) and anhydrous pyridine (50 mL) were added to the flask and the contents were stiπed at room temperature overnight. The reaction was checked by TLC (5% methanol/chloroform). If more than a trace of starting nucleoside was visible, more l-(3-dimethylaminopropyl)- 3-ethylcarbodiimide hydrochloride (2-5 mmol) was added to the reaction and stirring was continued for another day. When TLC showed complete disappearance of the starting nucleoside, the solution was concentrated by evaporation until a thick oil was formed. The oil was redissolved in chloroform (~ 200 mL) and transfer to a separatory funnel. The chloroform solution was washed with aqueous sodium bicarbonate (~ 100 mL x 2) and then water (~ 100 mL x 3). The funnel was slowly inverted to mix the two phases. The chloroform phase was collected and the aqueous phase was discarded. If an inseparable emulsion was formed, then either centrifugation (for small volumes) or (for large volumes) precipitation by addition of hexanes followed by filtration and redissolving the sticky precipitate back into chloroform can be performed. The chloroform solution was added to anhydrous magnesium sulfate and mixed to remove residual moisture from the solution. The magnesium sulfate was filtered off, the filtrated was washed with a small amount of chloroform and then the chloroform solution was evaporated to dryness. A light brown foam, containing a mixture of diester and nucleoside hemiester sodium salt, was formed and solidified. The hemiester sodium salt was converted into a more soluble pyridinium salt by dissolving the foam in pyridine (~ 50-100 mL) and then adding AG 50W- X4 W cation exchange resin (2 eq.). The mixture was stiπed for approximately 5 minutes and then the ion exchange resin was filtered off. The pyridine solution was evaporated to dryness. A light brown foam formed and solidified. The sold was dried under vacuum overnight to remove excess pyridine. Example 2 - P REPARATI ON O F 1 2 - D I M E TH O XY TRI T Y L - HYDROXYDO-DECANOIC ACID DERIVATIZED SUPPORTS This example describes the synthesis of a C 12 linker arm within the scope of the present invention and how it can be used to convert commercially available amino-derivatized supports into reusable hydroxyl-derivatized supports. 12-Hydroxydodecanoic acid (9.25 mmol) was coevaporated to dryness with pyridine (3x). Then pyridine (~ 40 mL) and dimethoxytrityl chloride (10.2 mmol) were added. After stirring overnight, the solution was concentrated (to 10 mL), diluted with CHC1 3 (50 mL), washed with aq. NH 4 HCO 3 (3x) and water (2x). The crude material was then purified on a silica gel column by elution with a 1 % TΕA/CHCI 3 - 4% MeOH/1 %TEA CHC1 3 gradient. The prodcut yield was 6.7 mmol (72%) of 12-dimethoxytrityl-hydroxydodecanoic acid as a brown oil. An amino functionalized support (0.5 g), 12-dimethoxytritylhydroxy- dodecanoic acid (0.2 mmol), 4-dimethylaminopyridine (0.1 mmol), l-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.6 mmol), triethylamine (0.1 mL), and pyridine (7 mL) were shaken at room temperature ( 16 h). The support was filtered off, washed, and dried. Linker loading was determined by trityl analysis and the results are provided in Table 1. Unreacted amino and hydroxyl groups on the derivatized support (if present) were then acetylated by treating the support with equal volumes 1 M acetic anhydride/2,6- lutidine/THF (Cap A) and 2M N-methylimidazole/THF (Cap B) reagents for 3 hours. The support was then filtered off, washed, and dried. Table 1- Loading Results Using 12-Dimethoxytrityl- hvdroxydodecanoic Acid Linker Arm Example 3 - DERIVATIZATION OF TOYOPEARL HW-65F SUPPORT WITH 1.4-BUTANEDIOL DIGLYCIDYL ETHER This Example describes how hydroxyl surface groups on commercially available Toyopearl HW65 supports are extended with a butane diglycidyl linker to create a reusable support. Toyopearl HW-65F vinyl alcohol/methacrylic acid copolymer was obtained as a slurry in 500 ml 20% ethanol/water. This slurry was evaporated to dryness to yield of 90 g of dry support. The hydroxyl content of the dry support was determined, in triplicate, by derivatization with dimethoxytrityl chloride/tetrabutylammonium perchlorate and trityl analysis, to be 1 ,095 μmol/g. The dry HW-65F support (25 g), 1.0 M aqueous NaOH solution containing 1 mg/mL NaBH 4 (100 mL) and 1 ,4-butanediol diglycidyl ether (75 mL) were shaken at room temperature (3.5 h). The support was filtered off and washed with water, acetonitrile, and then chloroform. After drying, DMT derivatization and analysis (M.P. Reddy and P.J. Voelker, 1988, Int. J. Peptide Protein Res. 31, 345-348, the contents of which are hereby incorporated by reference) of a sample indicated 902 μmol/g of remaining hydroxyl groups. Therefore, the epoxide loading was estimated to be 193 μmol/g. The epoxide denvatized support (25 g), benzoic anhydπde (51 g), 4- dimethylammopyndine (6.6 g) and anhydrous pyndine (180 mL) were shaken at room temperature (overnight) to benzoylate unreacted hydroxyl groups. The support was filtered off, washed (methanol, then chloroform), and dned. DMT denvatization and analysis indicated that the residual hydroxyl group loading had decreased to only 5 μmol/g. The benzoylated support (25 g), THF (140 mL), and 2.9 N aqueous HClO 4 (16.6 mL, 48 mmol) were shaken at room temperature (13 h). Trityl deπvatization and analysis of an aliquot showed an hydroxyl loading of 98 μmol g. Additional 2.9 N HClO 4 (34 mL) was added and shaking continued for another 3 h The support was filtered off, washed, and dned and a final tπtyl deπvatization and analysis indicated an hydroxyl loading of 103 μmol/g. Example 4 - S Y N T H E S I S O F O L I G O N U C L E O T I D E PHOSPHOROTHIOATES AND SUPPORT RECYCLING USING CHLOROACETIC ANHYDRIDE CAPPING. This Example provides expenments which illustrate the suitability of a vanety of different supports for repetitive oligonucleotide synthesis. The following reagents were installed on a Perkm-Elmer/Applied Biosystems 3944-column, 8-base position DNA synthesizer Ports #1-4: dA Bz , dG lBu , dC Bz , and T phosphoramidites (0.2 M solutions). Port #7 : 0.15 M 5'-dιmethoxytπty-N 6 -benzoyl-2'-deoxyadenosιne-3'-0-hydro- qumone-O.O'-diacetyl hemiester pyndinium salt and 0.15 M diisopropylethylamme in anhydrous acetonitnle Port #8: 0.15 M HBTU and 0 15M DMAP in anhydrous acetonitrile. Port #9- 0.45 M Tetrazole/acetomtπle. Port #10 28% Ammonium hydroxide. Port #11 : 1 M Chloroacetic anhydride in THF (Cap A reagent). Port #12: 1 M 2,6-Lutidine and 2 M N-methylimidazole in THF (Cap B reagent). Port #14: 5% (v/v) Dichloroacetic acid/l,2-dichloroethane. Port # 15: 0.05 M Beaucage reagent in acetonitrile. Up to four synthesis columns, each containing one of the supports listed in Table 2, were installed on the synthesizer and, if necessary, manually detritylated to deblock the hydroxyl linker arm. The synthesizer was then programmed to automatically execute the following steps: 1 : A "Begin" procedure consisting of a column wash, nucleoside coupling to the support by simultaneous addition (4.0 sec) of nucleoside hemiester (port #7) and coupling reagent (port #8) and a 600 sec wait, column wash, capping of unreacted hydroxyl sites (Cap A + B reagents, 300 sec), column wash, and priming of ports #1 , 2, 3, 4, and 9. Synthesis of the 20-base phosphorothioate oligonucleotide sequence dGCCC AAGCTGGCATCCGTCA (Trityl-off). 3: A 15 minute ammonium hydroxide hydrolysis step to cleave the oligonucleotide from the support. After completion of the ammonium hydroxide hydrolysis, the columns were removed from the synthesizer, manually treated with 0.05 M potassium carbonate/methanol solution (5 min), rinsed with methanol, dried by aspiration (5 min), re-installed on the synthesizer, and rinsed with anhydrous acetonitrile. The automated synthesis was then repeated (i.e., Steps 1, 2, and 3 above) using the same synthesis column a total of twelve times. The amount of trityl color released after the first detritylation step was collected and quantitated to determine the amount of nucleoside added to the support - the results are reported in Table 3. The released oligonucleotide solution was deprotected (55°C, 16 h), evaporated to removed ammonia, and quantitated by UV at 260 nm - the results are reported in Table 4. The coπect identity of the products, obtained from each of the results shown Table 4, was verified by electrophoresis and comparison to authentic material. Furthermore, no unusual impurities, attributable to the support recycling were present. These results confirmed that each of the nine supports used in this experiment could be reused and in several cases satisfactory results (comparable to new supports) were obtained, even after six or more uses. Example 5 - S Y N T H E S I S O F O L I G O N U C L E O T I D E PHOSPHOROTHIOATES AND SUPPORT RECYCLING USING METHOXYACETIC ANHYDRIDE CAPPING This Example illustrates the use of methoxyacetic anhydride as the capping reagent instead of chloroacetic anhydride used in the previous Examples. The automated DNA synthesizer was set-up with reagents, as described in Example 4, with the exception of the Cap A and B reagents, which were as follows: Port #10: 0.5 M Methoxyacetic anhydride and 0.5 M 2,6-lutidine in acetonitrile (Cap A). Port #12: 1 M N-Methylimidazole in acetonitrile (Cap B). The automated nucleoside derivatization, oligonucleotide synthesis, and support recycling procedure was then performed using the supports listed in Table 5 and the procedure described in Example 4. However, because of the greater stability of the methoxyacetyl group, the manual column regeneration step with 0.05M potassium carbonate/methanol was increased from 5 min to 15 min. The amount of trityl color released after the first detritylation step was collected and quantitated to determine the amount of nucleoside added to the support - the results are reported in Table 6. The released oligonucleotide solution was deprotected (55°C, 16 h), evaporated to removed ammonia, and quantitated by UV at 260 nm - the results are reported in Table 7. The composition of the products obtained in Table 7 was examined by gel electrophoresis and the expected products were obtained in each case. This indicated that methoxyacetic anhydride could also be used as a satisfactory capping reagent during the support recycling. Table 2 - Supports Used For Phosphorothioate Synthesis and Support Recycling *proprietary material supplied by Pharmacia Table 3 - Nucleoside loading obtained after repetitive synthesis on the same support O B O - > Table 4 - Amount of Crude Oligonucleotide Produced From Repetitive Syntheses on the Same Support Table 5 - Supports Used For Oligonucleotide Phosphorothioate Synthesis and Support Recycling O Table 6 - Nucleoside Loading Obtained After Repetitive Synthesis on the Same Support D O D Table 7 - Amount of Crude Oligonucleotide Produced From Repetitive Syntheses on the Same Support

Claims: What is claimed is: 1. A reusable linker arm for solid support oligonucleotide synthesis, the linker arm comprising the following formula: Z— O— T- [SUPPORT] wherein Z is a linker moiety and T is an organic radical. 2. The reusable linker arm defined in claim 1, wherein T contains at least one carbon. 3. The reusable linker arm defined in claim 1 , wherein T is a C,-C 300 organic moiety. 4. The reusable linker arm defined in claim 1 , wherein T is a C,-C 200 organic moiety. 5. The reusable linker arm defined in claim 1, wherein T is a C,-C 100 organic moiety. 6. The reusable linker arm defined in claims 1-5, wherein T is a saturated organic moiety. 7. The reusable linker arm defined in claims 1 -5 , wherein T is an unsaturated organic moiety. 8. The reusable linker arm defined in claim 1 , wherein T is a C,-C 300 organic moiety comprising at least one heteroatom selected from N and O. 9. The reusable linker arm defined in claims 1 - 8 , wherein the organic moiety comprises at least one moiety having the formula: O II -C- 10. The reusable linker arm defined in claims 1-8, wherein the organic moiety comprises at least one moiety having the formula: - N(H) - . 11. The reusable linker arm defined in claims 1-8. wherein the organic moiety comprises at least one moiety having the formula: O I I ■ N(H)C- 12. The reusable linker arm defined in claims 1 -8, wherein the organic moiety comprises at least one moiety having the formula: - C - O - C - . 13. The reusable linker arm defined in claims 1-8, wherein organic moiety comprises at least one moiety having the formula: O II — C-O- 14. The reusable linker arm defined in claims 1-13, wherein the organic moiety is unsubstituted. 15. The reusable linker arm defined in claim 14, wherein the organic moiety is substituted by at least one moiety selected from the group comprising a C,-C 40 alkyl group, a C 5 -C 40 aryl group, a C,-C 40 alkoxy group, a C,-C 40 ester group, a C,- C 40 hydroxy group, a C 2 -C 40 acrylate group and a C 5 -C 40 alkylaryl group. 16. The reusable linker arm defined in claims 1-15, wherein T has the formula: wherein q and s are the same or different and each is an integer having a value of 0-40 and r is an integer having a value of 1-200. 17. The reusable linker arm defined in claim 16, wherein q and s are the same or different and each is an integer having a value of 1-20 and r is an integer having a value of 1-150. 18. The reusable linker arm defined in claims 1-15, wherein T has the formula: wherein a is 0 or 1, Q is an organic moiety, R a is selected from -OH, -NH 2 , -NR and -OR wherein R is a protecting group and b is an integer having a value of 0- 40. 19 The reusable linker arm defined m claim 18, wherein a is 0 and R 8 is - OH 20 The reusable linker arm defined in claim 18, wherein a is 1 and R is -NR or -OR 21 The reusable linker arm defined in claims 18-20, wherein the protecting group is selected from the group compπsing acetyl, chloroacetyl, methoxyacetyl, t-butyl phenoxyacetyl, phenoxyacetyl, tπtyl, methoxytntyl, dimethoxytπtyl (DMT), dialkylphosphite, pivalyl-isobutyloxycarbonyl, /-butyldimethylsilyl, 9- phenylxanthen-9-yl (pixyl), tetrahydropyranyl, methoxvtetrahydropyranyl, methoxymethyl, benzyloxymethyl, methoxyethoxymethyl, methylthiomethyl, dialkylphosphate, levuhnyl, dimethylphenylsilyl, tnmethylsilyl, lsopropyl- dimethylsilyl, dnsopropylmethylsilyl, diethyhsopropylsilyl, tnisopropylsilyl, benzoyl, pivaloyl, trifluoroacetyl, allyl. benzyl, o-mtrobenzyl, o- hydroxystyryldimethylsilyl, 2-oxo- 1 ,2-dιphenylethyl, allyloxycarbonyl, monomethoxymethyl, mtroveratryloxycarbonyl, dimethoxybenzoin, dimethoxybenzoin carbonate, methylnitropiperonyl carbonate, fluorenyl- methoxycarbonyl, 2-phenylsulfonylethoxycarbony, fluorophenyl- methoxypipendmyl and mixtures thereof 22. The reusable linker arm defined in claim 18, wherein Q comprises a moiety having the formula: wherein q, r, s, t and u are the same or different and each is an integer having a value of 0-40 and R a is selected from the group comprising hydrogen, hydroxyl, a C,-C 40 alkyl group, a C 5 -C 40 aryl group, a C,-C 40 alkoxy group, a C,-C 40 ester group,a C,-C 40 hydroxy group, a C 2 -C 40 acrylate group, a C 5 -C 0 alkylaryl group, -NH 2 , -NHR and -OR, wherein R is a protecting group. 23. The reusable linker arm defined in claim 22, wherein s is 0, q, r and u are the same or different and each is an integer having a value of 1 - 10, t is an integer of 1-5 and R a is hydroxyl. 24. The reusable linker arm defined in claims 1-15, wherein T has the formula: wherein a is 0 or 1 , Q is an organic moiety, R a is selected from -OH, -NH 2 , -NR and -OR wherein R is a protecting group and b is an integer having a value of 0- 40. 25. The reusable linker arm defined in claim 24, wherein a is 0 and R 8 is -OH. 26. The reusable linker arm defined in claim 24, wherein a is 1 and R a is -NR or -OR. 27. The reusable linker arm defined m claim 18, wherein Q is a C,-C 100 organic moiety. 28. The reusable linker arm defined m claim 18, wherein Q is a saturated organic moiety. 29. The reusable linker arm defined in claim 18. wherein Q is an unsaturated organic moiety 30. The reusable linker arm defined in claim 18, wherein T is a C,-C ]00 organic moiety comprising at least one heteroatom selected from N and O. 31. The reusable linker arm defined m claims 27-30, wherein the organic moiety comprises at least one moiety having the formula. O I I -c- 32. The reusable linker arm defined m claims 27-30, wherein the organic moiety compπses at least one moiety having the formula: ■ N(H) - 33. The reusable linker arm defined m claims 27-30, wherein the organic moiety compπses at least one moiety having the formula: O II -N(H)C- 34. The reusable linker arm defined in claims 27-30, wherein the organic moiety comprises at least one moiety having the formula: - C - O - C - . 35. The reusable linker arm defined in claims 27-30, wherein organic moiety comprises at least one moiety having the formula: O II — C-O— . 36. The reusable linker arm defined in claim 27-35, wherein the organic moiety is unsubstituted. 37. The reusable linker arm defined in claim 27-35, wherein the organic moiety is substituted by at least one moiety selected from the group comprising a C,-C 40 alkyl group, a C 5 -C 40 aryl group, a C r C 40 alkoxy group, a C r C 40 ester group,a C,-C 40 hydroxy group, a C 2 -C 40 acrylate group and a C 5 -C 40 alkylaryl group. 38. The reusable linker arm defined in claim 18, wherein Q has the formula: wherein each of x, y and z is an integer having a value of 1-40. 39. The reusable linker arm defined in claims 1-38, wherein Z has the following formula: O O II II HO— C— CH,— CH 2 — C — 40. The reusable linker arm defined in claims 1-38, wherein Z has the following formula: O O I! II HO— C— CH 2 — O— CH 2 — C- 41. The reusable linker arm defined in claims 1-38, wherein Z has the following formula: O O II II HO— C— C- 42 The reusable linker arm defined m claims 1-38, wherein Z has the following foπnula wherein R 1 , R 2 and R^ are the same or different and are selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C ] -C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, R 4 and R 5 are the same or different and are selected from the group consisting of hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C.,-C 40 alkylaryl group, X 1 is selected from the group consisting of -O-, -S-, -C(O)-, -S(O) 2 - and -N(R)-, R is selected from the group compnsing hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, n is 0, 1 or 2. and one of A 1 and B 1 is selected from the group consisting of hydrogen, halide, a substituted or unsubstituted -C JQ alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, and the other of A 1 and B 1 has the formula whereinp is O or 1, X 2 is selected from the group consisting of -O-, -S-, -C(O)-, -S(O) 2 - and -N(R)-, R is selected from the group comprising hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 - C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, R 6 and R 7 are the same or different and are selected from the group comprising hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, and m is 0, 1 or 2. 43. The reusable linker arm defined in claim 42, wherein p is 0. 44. The reusable linker arm defined in claims 42-43, wherein B 1 is selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C,- C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group. 45. The reusable linker arm defined in claims 42-44, wherein each of R , R R >6 a „„ndJ τ R7 is hydrogen. 46. The reusable linker arm defined in claims 42-45, wherein each of m and n are 1. 47. The reusable linker arm defined in claims 42-46, wherein each of R 1 , R 2 and R is hydrogen. 48. The reusable linker arm defined in claims 42-47, wherein X 1 and X 2 are both -O-. 49. The reusable linker arm defined in claims 1-48, wherein SUPPORT is an inorganic substance. 50. The reusable linker arm defined in claim 49, wherein the inorganic substance is selected from the group consisting of silica, glass beads, porous glass, aluminosilicates, borosilicates, metal oxides, clays and mixtures thereof. 51. The reusable linker arm defined in claims 1 -48, wherein SUPPORT is an organic substance. 52. The reusable linker arm defined in claim 51, wherein the organic substance is a cross-linked polymer. 53. A reusable linker arm for solid support oligonucleotide synthesis, the linker arm comprising the following formula: NUCLEO SIDE— Z— O— T [SUPPORT] wherein Z is a linker moiety and T is an organic radical. 54. The reusable linker arm defined in claim 53, wherein T contains at least one carbon. 55. The reusable linker arm defined in claim 53, wherein T is a C 1 -C 300 organic moiety. 56. The reusable linker arm defined in claim 53, wherein T is a C r C 200 organic moiety. 57. The reusable linker arm defined in claim 53, wherein T is a Cι-C 100 organic moiety. 58. The reusable linker arm defined in claims 53-57, wherein T is a saturated organic moiety. 59. The reusable linker arm defined in claims 53-57, wherein T is an unsaturated organic moiety. 60. The reusable linker arm defined in claims 53-57, wherein T is a C,-C 300 organic moiety comprising at least one heteroatom selected from N and O. 61. The reusable linker arm defined in claims 53-60, wherein the organic moiety comprises at least one moiety having the formula: O II -C- 62. The reusable linker arm defined in claims 53-60, wherein the organic moiety comprises at least one moiety having the formula: - N(H) - . 63. The reusable linker arm defined in claims 53-60, wherein the organic moiety comprises at least one moiety having the formula: O II • N(H)C- 64. The reusable linker arm defined in claims 53-60, wherein the organic moiety comprises at least one moiety having the formula: - C - O - C - . 65. The reusable linker arm defined in claims 53-60, wherein organic moiety comprises at least one moiety having the formula: O II — C-O — . 66. The reusable linker arm defined in claims 53-65, wherein the organic moiety is unsubstituted. 67. The reusable linker arm defined in claims 53-65, wherein the organic moiety is substituted by at least one moiety selected from the group comprising a C,-C 40 alkyl group, a C 5 -C 40 aryl group, a C,-C 40 alkoxy group, a C r C 40 ester group,a C,-C 40 hydroxy group, a C 2 -C 40 acrylate group and a C 5 -C 40 alkylaryl group. 68. The reusable linker arm defined in claims 53-67, wherein T has the formula: wherein q and s are the same or different and each is an integer having a value of 0-40 and r is an integer having a value of 1-200. 69. The reusable linker arm defined in claim 68, wherein q and s are the same or different and each is an integer having a value of 1-20 and r is an integer having a value of 1 - 150. 70. The reusable linker arm defined in claims 53-67, wherein T has the formula: R a — £Q3-CH 2 — CH-CH 2 — O-£cH 2 jJ- wherein a is 0 or 1, Q is an organic moiety, R a is selected from -OH, -NH 2 , -NR and -OR wherein R is a protecting group and b is an integer having a value of 0- 40. 71. The reusable linker arm defined in claim 70, wherein a is 0 and R 8 is - OH.. 72. The reusable linker arm defined in claim 70, wherein a is 1 and R a is -NR or -OR. 73. The reusable linker arm defined in claims 70-72, wherein the protecting group is selected from the group comprising acetyl, chloroacetyl, methoxyacetyl, t-butyl phenoxyacetyl, . trityl, methoxytrityl, dimethoxytrityl (DMT), dialkylphosphite, pivalyl-isobutyloxycarbonyl, -butyldimefhylsilyl, phenoxyacetal, 9-phenylxanthen-9-yl (pixyl), tetrahydropyranyl, methoxytetrahydropyranyl, methoxymethyl, benzyloxymethyl, methoxyethoxymethyl, methylthiomethyl, dialkylphosphate, levulinyl, dimethylphenylsilyl, trimethylsilyl, isopropyldimethylsilyl, diisopropylmethylsilyl, diethylisopropylsilyl, triisopropylsilyl, benzoyl, pivaloyl, trifluoroacetyl, allyl, benzyl, o-nitrobenzyl, o-hydroxystyryldimethylsilyl, 2-oxo- 1 , 2 -diphenylethyl . allyloxycarbonyl, monomethoxymethyl, nitroveratryloxycarbonyl, dimethoxybenzoin, dimethoxybenzoin carbonate, methylnitropiperonyl carbonate, fluorenylmethoxycarbonyl, 2-phenylsulfonyl- ethoxycarbony, fluorophenyl-methoxypiperidinyl and mixtures thereof. 74. The reusable linker arm defined in claim 70, wherein Q comprises a moiety having the formula: wherein q, r, s, t and u are the same or different and each is an integer having a value of 0-40 and R a is selected from the group comprising hydrogen, hydroxyl, a C,-C 40 alkyl group, a C 5 -C 40 aryl group, a C,-C 40 alkoxy group, a C,-C 40 ester group, a C,-C 40 hydroxy group, a C 2 -C 40 acrylate group, a C -C 40 alkylaryl group, -NH 2 , -NHR and -OR, wherein R is a protecting group. 75. The reusable linker arm defined in claim 74, wherein s is 0, q, r and u are the same or different and each is an integer having a value of l-10, t is an integer of 1-5 and R a is hydroxyl. 76 The reusable linker arm defined in claim 70, wherein T has the formula R a — F L —Q^ — ' aCH 2 — CH-CH " ,— 0 i—CH 2 —i- v. wherein a is 0 or 1, Q is an organic moiety, R a is selected from -OH, -NH,, -NR and -OR wherein R is a protecting group and b is an integer having a value of 0- 40 77 The reusable linker arm defined in claim 76, wherein a is 0 and R 8 is -OH 78 The reusable linker arm defined in claim 76, wherein a is 1 and R is -NR or -OR 79 The reusable linker arm defined m claims 53-78, wherein Q is a C,-C 100 organic moiety 80 The reusable linker arm defined in claims 53-78, wherein Q is a saturated organic moiety 81 The reusable linker arm defined m claims 53-78, wherein Q is an unsaturated organic moiety 82 The reusable linker arm defined in claims 53-78, wherein T is a C,-C 100 organic moiety compnsmg at least one heteroatom selected from N and O 83 The reusable linker arm defined in claims 76-82, wherein the organic moiety compπses at least one moiety having the formula O II -C — 84. The reusable linker arm defined in claims 76-82, wherein the organic moiety comprises at least one moiety having the formula: - N(H) - . 85. The reusable linker arm defined in claims 76-82, wherein the organic moiety comprises at least one moiety having the formula: O II • N(H)C- 86. The reusable linker arm defined in claims 76-82. wherein the organic moiety comprises at least one moiety having the formula: - C - O - C - . 87. The reusable linker arm defined in claims 76-82, wherein organic moiety comprises at least one moiety having the formula: O II — C-O — . 88. The reusable linker arm defined in claims 76-87, wherein the organic moiety is unsubstituted. 89. The reusable linker arm defined in claims 76-87, wherein the organic moiety is substituted by at least one moiety selected from the group comprising a C,-C 40 alkyl group, a C 5 -C 40 aryl group, a C,-C 40 alkoxy group, a C,-C 0 ester group, a C,-C 40 hydroxy group, a C 2 -C 40 acrylate group and a C 5 -C 40 alkylaryl group. 90. The reusable linker arm defined in claim 53, wherein Q has the formula: wherein each of x, y and z is an integer having a value of 1-40. 91. The reusable linker arm defined in claims 53-90, wherein Z has the following formula: O O II II — C— CH 2 — CH 2 — C — 92. The reusable linker arm defined in claims 53-90, wherein Z has the following formula: O O II II -C— CH 2 — O— CH 2 — C — 93. The reusable linker arm defined in claims 53-90, wherein Z has the following formula: O O II II — C— C- 94. The reusable linker arm defined in claims 53-90, wherein Z has the following formula: wherein: R 1 , R 2 and R 3 are the same or different and are selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group; R 4 and R 3 are the same or different and are selected from the group consisting of hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group; X 1 is selected from the group consisting of -O-, -S-, -C(O)-, -S(O) 2 - and -N(R)-; R is selected from the group comprising hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group; n is 0, 1 or 2; and one of A 1 and B 1 is selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, and the other of A 1 and B 1 has the formula: wherein p is O or 1, X 2 is selected from the group consisting of -O-, -S-, -C(O)-, -S(O) 2 - and -N(R)-, R is selected from the group comprising hydrogen, a substituted or unsubstituted C ,-C 20 alkyl group, a substituted or unsubstituted C 5 - C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, R 6 and R' are the same or different and are selected from the group comprising hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, and m is 0, 1 or 2. 95. The reusable linker arm defined in claim 94, wherein p is 0. 96. The reusable linker arm defined in claims 94-95, wherein B 1 is selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C,- C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group. 97. The reusable linker arm defined in claims 94-96, wherein each of R 4 , R 5 , R 6 and R is hydrogen. 98. The reusable linker arm defined in claims 94-97, wherein each of m and n are 1. 99. The reusable linker arm defined in claims 94-98, wherein each of R 1 , R 2 and R 3 is hydrogen. 100. The reusable linker arm defined in claims 94-99, wherein X 1 and X 2 are both -0-. 101. The reusable linker arm defined in claims 53-100, wherein SUPPORT is an inorganic substance. 102. The reusable linker arm defined in claim 101, wherein the inorganic substance is selected from the group consisting of silica, glass beads, porous glass, aluminosilicates, borosilicates, metal oxides, clays and mixtures thereof. 103. The reusable linker arm defined in claims 53-100, wherein SUPPORT is an organic substance. 104. The reusable linker arm defined in claim 103, wherein the organic substance is a cross-linked polymer. 105. The reusable linker arm defined in claims 53-104, wherein NUCLEOSIDE is a moiety selected from one of the following formulae: wherein R 8 and R 10 are the same or different and are hydrogen or a protecting group, R 9 is hydrogen or -OR" wherein R" is hydrogen or a protecting group, and B * is a nucleic acid base 106 A process for production of a reusable linker arm for oligonucleotide synthesis having the following formula Z— O— T [SUPPORT] wherein Z is a linker moiety and T is an organic radical, the process compnsmg the step of reacting together the compound of Formulae I and II Z— OH HO- T [SUPPORT] (I) (ID wherein Z and T are as defined above 107 The process defined m claim 106. wherein T contains at least one carbon 108 The process defined m claim 106. wherein T is a -C JQQ organic moiety 109 The process defined in claim 106, wherein T is a C,-C 200 organic moiety 110 The process defined in claim 106, wherein T is a C,-C 100 organic moiety 111 The process defined in claims 106- 110, wherein T is a saturated organic moiety 112 The process defined in claims 106-110, wherein T is an unsaturated organic moiety 113 The process defined m claims 106-112, wherein T is a C,-C 300 organic moiety compnsmg at least one heteroatom selected from N and O 114 The process defined in claims 106-113, wherein the organic moiety compnses at least one moiety having the formula O II — C- 115. The process defined in claims 106-113, wherein the organic moiety comprises at least one moiety having the formula: - N(H) - . 116. The process defined in claims 106-113, wherein the organic moiety comprises at least one moiety having the formula: O II ■ N(H)C- 117. The process defined in claims 106-113, wherein the organic moiety comprises at least one moiety having the formula: - C - O - C - . 118. The process defined in claims 106-113, wherein organic moiety comprises at least one moiety having the formula: O I I ■ C-O- 119 The process defined in claims 106-118, wherein the organic moiety is unsubstituted. 120 The process defined in claims 106-118, wherein the organic moiety is substituted by at least one moiety selected from the group compnsmg a C,-C 40 alkyl group, a C 3 -C 40 aryl group, a C,-C 0 alkoxy group, a C,-C 40 ester group, a C,- C 40 hydroxy group, a C 2 -C 40 acrylate group and a C,-C 40 alkylaryl group 121 The process defined in claims 106-120, wherein T has the formula. wherein q and s are the same or different and each is an integer having a value of 0-40 and r is an integer having a value of 1-200 122 The process defined in claim 121, wherein q and s are the same or different and each is an integer having a value of 1 -20 and r is an integer having a value of 1-150 123 The process defined in claims 106-120, wherein T has the formula: wherein a is 0 or 1, Q is an organic moiety, R a is selected from -OH, -NH 2 , -NR and -OR wherein R is a protecting group and b is an integer having a value of 0- 40. 124. The reusable linker arm defined in claim 123, wherein a is 0 and R δ is - OH.. 125. The reusable linker arm defined in claim 123. wherein a is 1 andR a is -NR or -OR. 126. The process defined in claims 123-125, wherein the protecting group is selected from the group comprising acetyl, chloroacetyl, methoxyacetyl, t-butyl phenoxyacetyl, trityl, methoxytrityl, dimethoxytrityl (DMT), dialkylphosphite, pivalyl-isobutyloxycarbonyl, r-butyldimethylsilyl. phenoxyacetal, 9- phenylxanthen-9-yl (pixyl), tetrahydropyranyl, methoxytetrahydropyranyl, methoxymethyl, benzyloxymethyl, methoxyethoxymethyl, methylthiomethyl, dialkylphosphate, levulinyl, dimethylphenylsilyl, trimethylsilyl, isopropyl- dimethylsilyl, diisopropylmethylsilyl, diethylisopropylsilyl, triisopropylsilyl, benzoyl, pivaloyl, trifluoroacetyl, allyl, benzyl, o-nitrobenzyl, o- hydroxystyryldimethylsilyl, 2-oxo- 1 ,2-diphenylethyl, allyloxycarbonyl, monomethoxymethyl, nitroveratryloxycarbonyl, dimethoxybenzoin, dimethoxybenzoin carbonate, methylnitropiperonyl carbonate, fluorenyl- methoxycarbonyl, 2-phenylsulfonylethoxycarbony, fluorophenyl- methoxypiperidinyl and mixtures thereof. 127. The process defined in claims 106-126, wherein Z has the following formula: O O II II HO— C— CH 2 — CH 2 — C — 128. The process defined in claims 106-126, wherein Z has the following formula: O O II II HO— C— CH,— O— CH 7 — C- 129. The process defined in claims 106-126, wherein Z has the following formula: O O II II HO— C— C — 130. The process defined in claims 106-126, wherein Z has the following formula: wherein: R 1 , R 2 and R 3 are the same or different and are selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C,-C 40 alkylaryl group; R 4 and R 3 are the same or different and are selected from the group consisting of hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group; X 1 is selected from the group consisting of -0-, -S-, -C(O)-, -S(O) 2 - and -N(R)-; R is selected from the group comprising hydrogen, a substituted or unsubstituted C j -C^ alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group; n is 0. 1 or 2; and one of A 1 and B 1 is selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted -C 40 alkylaryl group, and the other of A 1 and B 1 has the formula: wherein p is O or 1, X 2 is selected from the group consisting of -O-, -S-, -C(O)-, -S(O) 2 - and -N(R)-, R is selected from the group comprising hydrogen, a substituted or unsubstituted C r C 20 alkyl group, a substituted or unsubstituted C 5 - C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, R 6 and R 7 are the same or different and are selected from the group comprising hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, and m is 0, 1 or 2. 131. The process defined in claim 130, wherein p is 0. 132. The process defined in claims 130-131, wherein B 1 is selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group. 133. The process defined in claims 130-132, wherein each of R 4 , R 5 , R 6 andR 7 is hydrogen. 134. The process defined in claims 130-133, wherein each of m and n are 1. 135. The process defined in claims 130-134, wherein each of R 1 , R 2 and R 3 is hydrogen. 136. The process defined in claims 130-135, wherein X 1 and X 2 are both -O-. 137. The process defined in claims 106-136, wherein SUPPORT is an inorganic substance. 138. The process defined in claim 137, wherein the inorganic substance is selected from the group consisting of silica, glass beads, porous glass, aluminosilicates, borosilicates, metal oxides, clays and mixtures thereof. 139. The process defined in claims 106-136, wherein SUPPORT is an organic substance. 140. The process defined in claim 139, wherein the organic substance is a cross-linked polymer. 141. The process defined in claims 106-140, wherein the process is conducted in the presence of an activating agent. 142. The process defined in claim 141, wherein the acitivating agent comprises at least one member selected from the group comprising an acid chloride; an active ester (e.g., nitrophenyl, nitrophenylthio, trichlorophenyl, trifluorophenyl, pentachlorophenyl, pentafluorophenyl, or 3-hydroxy-2,3-dihy ro-4-oxo- benzotriazine esters); an active hydroxylamine ester (e.g., N-hydroxyphthalimide or N-hydroxysuccinimide); acid anhydride and mixed anhydride. 143. The process defined in claim 141, wherein the activating agent comprises at least one member selected from the group comprising arylsulfonyl chlorides (e.g., benzenesulfonyl chloride (BS-C1), mesitylenesulfonyl chloride (MS-C1), triisopropylsulfonylchloride (TPS-C1)); active arylsulfonyl esters (e.g., imidazole, triazole, nitrotriazole, ortetrazole esters ofBS-Cl, MS-C1 or TPS-C1); 2-ethoxy- l-(ethoxycarbonyl)-l,2-dihydroqumoline (EEDQ); acyl carbonates; 1,1'- (carbonyldioxy)dibenzotriazoles; chlorotrimethylsilane; carbodiimides (e.g., dicyclohexylcarbodiimide (DCC), 1 -(3-dimethylaminopropyl)-ethylcarbodiimide (DEC), diisopropylcarbodiimide (DIC)) either alone or in combination with auxiliary nucleophiles (e.g., 1-hydroxybenzotriazole (HOBt), l-hydroxy-7- azabenzotriazole (HOAt), N-hydroxysuccinimide (HOSu), or 3-hydroxy-3,4- dihydro-l,2,3-benzotriazin-4-one (HOObt)) and/or catalysts (e.g., 4- dimethylaminopyridine (DMAP) or N-methylimidazole (NMI)); or uronium salts (e.g., tetramethyluronium chloride (TMU-Cl), 2-(lH-benzotriazol- 1 -yl)-l , 1,3,3- tetramethyluronium hexafluorophosphate (HBTU), 2-(lH-benzotriazol-l-yl)- 1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU), 2-succinimido-l, 1,3,3- tetramethyluronium tetrafluoroborate (TSTU), 2-(3,4-dihydro-4-oxo- 1,2,3- benzotriazin-3-yl)- 1,1,3 ,3 -tetramethyluronium tetrafluoroborate (TDBTU), 2-(2- oxo-l(2H)-pyridyl- 1,1, 3, 3 -tetramethyluronium tetrafluoroborate (TPTU), 2-(5- norbornene-2,3-dicarboximido)-l,l,3,3-tetramethyluronium tetrafluoroborate (TNTU), O-(7-azabenzotriazol- 1 -yl)- 1 ,3-dirnethyl- 1 ,3-dimethyleneuronium hexafluorophosphate (HAMDU), O-(7-azabenzotriazol- 1 -yl)- 1 ,3-dimethyl- 1 ,3-tri- methyleneuronium hexafluorophosphate (HAMTU), O-(7-azabenzotriazol- 1 -yl)- l,l,3,3-bis(pentamethylene)uronium hexafluorophosphate (HAPipU), O-(7- azabenzotriazol- 1 -yl)- 1 , 1 ,3 ,3-bis(tetramethylene)uronium hexafluorophosphate (HAPyU), O-(7-azabenzotriazol- l -yl)- 1 , 1 , 3, 3 -tetramethyluronium hexafluorophosphate (HATU)) either alone or in combination with auxiliary nucleophiles (i.e., 1-hydroxybenzotriazole (HOBt), l-hydroxy-7-azabenzotriazole (HOAt), N-hydroxysuccinimide (HOSu), or 3-hydroxy-3,4-dihydro-1.2,3- benzotriazin-4-one (HOObt)) and/or catalysts (e.g., 4-dimethylaminopyridine (DMAP) or N-methylimidazole (NMI)) orphosphonium salts (e.g., benzotriazol- 1 -yl-oxytris(dimethylamino)phosphonium hexafluorophosphate (BOP), benzotriazole- 1 -yl-oxy-trispyπolidinophosphonium hexafluorophosphate (PyBOP), 2-(benzotriazol- l -yl)oxy- l ,3-dimethylimidazolidinium hexafluorophosphate (BOI), bromo tris(pyrrolidino)phosphonium hexafluorophosphate (PyBroP), 7-azabenzotriazol- l -yloxytris- (dimethylamino)phosphonium hexafluorophosphate (AOP), and 7- azabenzotriazol-l-yloxytris(pyπolidino)phosphonium hexafluorophosphate (PyAOP)) either alone or in combination with auxiliary nucleophiles and/or catalysts. 144. A process for production of a reusable linker arm for oligonucleotide synthesis having the following formula: NUCLEOSIDE— Z—O—T [SUPPORT] wherein Z is a linker moiety and T is an organic radical, the process comprising the step of reacting together the compounds of Formulae I, II and III: HO- Z-OH HO- T— [SUPPORT] (i) (π) NUCLEOSIDE- OH (in) wherein Z and T are as defined above. 145. The process defined in claim 144, wherein T contains at least one carbon. 146. The process defined in claim 144, wherein T is a C,-C 300 organic moiety. 147. The process defined in claim 144, wherein T is a C,-C 200 organic moiety. 148. The process defined in claim 144, wherein T is a C,-C 100 organic moiety. 149. The process defined in claims 144-148, wherein T is a saturated organic moiety. 150. The process defined in claims 144-148, wherein T is an unsaturated organic moiety. 151. The process defined in claims 144-148, wherein T is a C [ -C 300 organic moiety comprising at least one heteroatom selected from N and O. 152. The process defined in claims 144-151, wherein the organic moiety comprises at least one moiety having the formula: O II — C- 153. The process defined in claims 144-151, wherein the organic moiety comprises at least one moiety having the formula: N(H) - 154. The process defined in claims 144-151, wherein the organic moiety comprises at least one moiety having the formula: O II ■ N(H)C- 155. The process defined in claims 144-151, wherein the organic moiety comprises at least one moiety having the formula: - C - O - C - . 156. The process defined in claims 144- 151, wherein organic moiety comprises at least one moiety having the formula: O II -C-O- 157. The process defined claims 144-156, wherein the organic moiety is unsubstituted. 158. The process defined m claims 144-156, wherein the organic moiety is substituted by at least one moiety selected from the group comprising a C,-C 40 alkyl group, a C,-C 40 aryl group, a C,-C 40 alkoxy group, a C,-C 40 ester group,a C,- C 40 hydroxy group, a C 2 -C 40 acrylate group and a C 3 -C 40 alkylaryl group. 159. The process defined in claims 144-158, wherein T has the formula: - CH 2 ^ — o-CH 2 — CH 2 — O^— [CH 2 ^- wherein q and s are the same or different and each is an integer having a value of 0-40 and r is an integer having a value of 1-200. 160. The process defined in claim 159, wherein q and s are the same or different and each is an integer having a value of 1 -20 and r is an integer having a value of 1-150. 161. The process defined in claim 144-158, wherein T has the formula: wherein a is 0 or 1, Q is an organic moiety, R a is selected from -OH, -NH 2 , -NR and -OR wherein R is a protecting group and b is an integer having a value of 0- 40. 162. The reusable linker arm defined in claim 161, wherein a is 0 and R b is - OH.. 163. The reusable linker arm defined in claim 161, wherein a is 1 and R a is -NR or -OR. 164. The process defined in claims 161-163, wherein the protecting group is selected from the group comprising acetyl, chloroacetyl, methoxyacetyl, t-butyl phenoxyacetyl, trityl, methoxytrityl, dimethoxytrityl (DMT), dialkylphosphite, pivalyl-isobutyloxycarbonyl, r-butyldimethylsilyl, phenoxyacetal. 9- phenylxanthen-9-yl (pixyl), tetrahydropyranyl, methoxvtetrahydropyranyl, methoxymethyl, benzyloxymethyl, methoxyethoxymethyl, methylthiomethyl, dialkylphosphate, levulinyl, dimethylphenylsilyl, trimethylsilyl, isopropyl- dimethylsilyl, diisopropylmethylsilyl, diethyhsopropylsilyl, triisopropylsilyl, benzoyl, pivaloyl, trifluoroacetyl, allyl, benzyl, o-nitrobenzyl, o- hydroxystyryldimethylsilyl, 2-oxo- 1 ,2-diphenylethyl, allyloxycarbonyl, monomethoxymethyl, nitroveratryloxycarbonyl, dimethoxybenzoin, dimethoxybenzoin carbonate, methylnitropiperonyl carbonate, fluorenyl- methoxycarbonyl, 2-phenylsulfonylethoxycarbony, fluorophenyl- methoxypiperidinyl and mixtures thereof. 165. The process defined in claims 144-164, wherein Z has the following formula: O O II II HO— C— CH 2 — CH 2 — C — 166. The process defined in claims 144-164, wherein Z has the following formula: O O HO— C— CH 7 — O— CH 7 — C — 167. The process defined in claims 144-164, wherein Z has the following formula: O O II II HO— C— C- 168. The process defined in claims 144-164, wherein Z has the following formula: wherein: R 1 , R 2 and R 3 are the same or different and are selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group; R 4 and R 3 are the same or different and are selected from the group consisting of hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group; X 1 is selected from the group consisting of -O-, -S-, -C(O)-, -S(O) 2 - and -N(R)-; R is selected from the group comprising hydrogen, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group; n is 0, 1 or 2; and one of A 1 and B 1 is selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, and the other of A 1 and B 1 has the formula: whereinp is O or 1, X 2 is selected from the group consisting of -O-, -S-, -C(O)-, -S(O) 2 - and -N(R)-, R is selected from the group comprising hydrogen, a substituted or unsubstituted C , -C 20 alkyl group, a substituted or unsubstituted C 5 - C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, R 6 and R 7 are the same or different and are selected from the group comprising hydrogen, a substituted or unsubstituted C r C 20 alkyl group, a substituted or unsubstituted C 5 -C 30 aryl group and a substituted or unsubstituted C 5 -C 40 alkylaryl group, and m is 0. 1 or 2. 169. The process defined in claim 168, wherein p is 0. 170. The process defined in claims 168-169, wherein B 1 is selected from the group consisting of hydrogen, halide, a substituted or unsubstituted C,-C 20 alkyl group, a substituted or unsubstituted C,-C 30 aryl group and a substituted or unsubstituted C < -C 40 alkylaryl group. 171. The process defined in claims 168-170, wherein each of R 4 , R 5 , R 6 and R 7 is hydrogen. 172. The process defined in claims 168-171, wherein each of m and n are 1. 173. The process defined in claims 168-172, wherein each of R 1 , R 2 and R 3 is hydrogen. 174. The process defined in claims 168-172, wherein X 1 and X 2 are both -O-. 175. The process defined in claims 144-174, wherein SUPPORT is an inorganic substance. 176. The process defined in claim 175. wherein the inorganic substance is selected from the group consisting of silica, glass beads, porous glass, aluminosilicates, borosilicates, metal oxides, clays and mixtures thereof. 177. The process defined in claims 144-174, wherein SUPPORT is an organic substance. 178. The process defined in claim 177, wherein the organic substance is a cross-linked polymer. 179. The process defined in claims 144-178, wherein the process is conducted in the presence of an activating agent. 180. The process defined in claim 179, wherein the acitivating agent comprises at least one member selected from the group comprising an acid chloride; an active ester (e.g., nitrophenyl, nitrophenylthio, trichlorophenyl, trifluorophenyl, pentachlorophenyl, pentafluorophenyl, or 3-hydroxy-2,3-dihydro-4-oxo- benzotriazine esters); an active hydroxylamine ester (e.g., N-hydroxyphthalimide or N-hydroxysuccinimide); acid anhydride and mixed anhydride. 181. The process defined in claim 179, wherein the activating agent comprises at least one member selected from the group comprising arylsulfonyl chlorides (e.g., benzenesulfonyl chloride (BS-C1), mesitylenesulfonyl chloride (MS-C1), triisopropylsulfonylchloride (TPS-C1)); active arylsulfonyl esters (e.g., imidazole, triazole, nitrotriazole, or tetrazole esters of BS-C1, MS-C1 or TPS-C1); 2-ethoxy- l-(ethoxycarbonyl)-1.2-dihydroquinoline (EEDQ); acyl carbonates; 1,1'- (carbonyldioxy)dibenzotriazoles; chlorotrimethylsilane; carbodiimides (e.g., dicyclohexylcarbodiimide (DCC), 1 -(3-dimethylaminopropyl)-ethylcarbodiimide (DEC), diisopropylcarbodiimide (DIC)) either alone or in combination with auxiliary nucleophiles (e.g., 1 -hydroxybenzotriazole (HOBt), l-hydroxy-7- azabenzotriazole (HOAt), N-hydroxysuccinimide (HOSu), or 3-hydroxy-3,4- dihydro-l,2,3-benzotriazin-4-one (HOObt)) and/or catalysts (e.g., 4- dimethylaminopyridine (DMAP) or N-methylimidazole (NMI)); or uronium salts (e.g., tetramethyluronium chloride (TMU-C1), 2-(lH-benzotriazol- 1 -yl)-l , 1 ,3,3- tetramethyluronium hexafluorophosphate (HBTU), 2-(lH-benzotriazol-l-yl)- 1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU), 2-succinimido-l, 1,3,3- tetramethyluronium tetrafluoroborate (TSTU), 2-(3,4-dihydro-4-oxo- 1,2,3- benzotriazin-3-yl)- 1 , 1 ,3, 3 -tetramethyluronium tetrafluoroborate (TDBTU), 2-(2- oxo-l(2H)-pyridyl-l,l,3,3-tetramethyluronium tetrafluoroborate (TPTU), 2-(5- norbornene-2,3-dicarboximido)-l,l,3,3-tetramethyluronium tetrafluoroborate (TNTU), O-(7-azabenzotriazol- 1 -yl)- 1 ,3-dimethyl- 1 ,3-dimethyleneuronium hexafluorophosphate (HAMDU), O-(7-azabenzotriazol-l-yl)-l,3-dimethyl-l,3-tri- methyleneuronium hexafluorophosphate (HAMTU), O-(7-azabenzotriazol- 1 -yl)- l,l,3,3-bis(pentamethylene)uronium hexafluorophosphate (HAPipU), O-(7- azabenzotriazol- 1 -yl)- 1 , 1 ,3 ,3-bis(tetramethylene)uronium hexafluorophosphate (HAPyU), O-(7-azabenzotriazol- l -yl)- 1 , 1 , 3, 3 -tetramethyluronium hexafluorophosphate (HATU)) either alone or in combination with auxiliary nucleophiles (i.e., 1-hydroxybenzotriazole (HOBt), l-hydroxy-7-azabenzotriazole (HOAt), N-hydroxysuccinimide (HOSu), or 3-hydroxy-3,4-dihydro-l,2,3- benzotriazin-4-one (HOObt)) and/or catalysts (e.g., 4-dimethylaminopyridine (DMAP) or N-methylimidazole (NMI)) orphosphonium salts (e.g., benzotriazol- 1 -yl-oxytris(dimethylamino)phosphonium hexafluorophosphate (BOP), benzotriazole-1-yl-oxy-trispyrrolidinophosphonium hexafluorophosphate (PyBOP), 2-(benzotriazol- l -yl)oxy- l ,3-dimethylimidazolidinium hexafluorophosphate (BOI), bromo tris(pyrrolidino)phosphonium hexafluorophosphate (PyBroP), 7-azabenzotriazol- l -yloxytris- (dimethylamino)phosphonium hexafluorophosphate (AOP), and 7- azabenzotriazol- 1 -yloxytris(pyπolidino)phosphonium hexafluorophosphate (PyAOP)) either alone or in combination with auxiliary nucleophiles and/or catalysts. 182. The process defined in claims 144-181, wherein NUCLEOSIDE is a moiety selected from one of the following formulae: wherein R 8 and R 10 are the same or different and are hydrogen or a protecting group, R 9 is hydrogen or -OR 11 wherein R 11 is hydrogen or a protecting group, and B * is a nucleic acid base. 183. The process defined in claims 144-182, wherein the compounds of Formulae I and II are initially reacted to form a conjugate which is reacted with the compound of Formula III. 184. The process defined in claims 144-182, wherein compounds of Formulae I and III are initially reacted to form a conjugate which is reacted with the compound of Formula II. 185. A process for producing an oligonucleotide having a desired sequence comprising the steps of: (i) reacting a linker arm having the formula: NUCLEOSΓDE— z— o— T — [SUPPORT] wherein Z is a linker moiety and T is an organic radical, with at least one oligonucleoside base until an oligonucleotide having the desired sequence is produce; (ii) cleaving the oligonucleotide having the desired sequence to produce a free oligonucleotide have the desired sequence; and a used linker arm; and (iii) recycling the used linker arm to Step (i). 186. The process defined in claim 185, wherein the used linker arm produced in Step (ii) has the formula: Z— O— T [SUPPORT] wherein Z is a linker moiety and T is an organic radical. 187. The process defined in claims 185-186, wherein Step (iii) comprises the step of converting the used linker arm to a linker arm having the formula: NUCLEOSIDE— Z—O—T [SUPPORT] wherein Z is a linker moiety and T is an organic radical.

Inventors: PON RICHARD T, YU SHUYUAN, PON, RICHARD, T., YU, SHUYUAN
Applicants: PON RICHARD T, UNIV TECHNOLOGIES INT, YU SHUYUAN, PON, RICHARD, T., UNIVERSITY TECHNOLOGIES INTERNATIONAL INC., YU, SHUYUAN
Application year: 1999
Main classification: C07H21
IPC codes: C07H21