Patent ID: 8450467

Claim:
A process of making a ligand-containing conjugate having the structure shown in formula (I): the process comprising the step of: reacting a hydroxyproline derivative containing one or more tether precursors containing Q, and a ligand moiety containing R, wherein: A and B are each independently for each occurrence O, N(R N ) or S; X and Y are each independently for each occurrence H, a protecting group, a phosphate group, a phosphodiester group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, —P(Z′)(Z″)O-nucleoside, —P(Z′)(Z″)O-oligonucleotide, a lipid, a PEG, a steroid, a polymer, a nucleotide, annucleoside, —P(Z′)(Z″)O—R 1 —Q′—R 2 —OP(Z′″)(Z′″)O—oligonucleotide, or an oligonucleotide, —P(Z′)(Z″)-formula (I), —P(Z′)(Z″)— or -Q-R; R is L′ or has the structure shown in formula (II)-(V) q 2A , q 2B , q 3A , q 3B , q 4A , q 4B , q 5A , q 5B and q 5C represent independently for each occurrence 0-20 and wherein the repeating unit can be the same or different; Q and Q′ are independently for each occurrence absent, —(P 7 -Q 7 -R 7 ) p -T 7 - or -T 7 -Q 7 -T 7′ -B-T 8′ -Q 8 -T 8 ; P 2A , P 2B , P 3A , P 3B , P 4A , P 4B , P 5A , P 5B , P 5C , P 7 , T 2A , T 2B , T 3A , T 3B , T 4A , T 4B , T 4A , T 5B , T 5C , T 7 , T 7′ , T 8 and T 8′ are each independently for each occurrence absent, CO, NH, O, S, OC(O), NHC(O), CH 2 , CH 2 NH or CH 2 O; B is —CH 2 —N(B L )—CH 2 —; B L is -T B -Q B -T B′ -R x ; Q 2A , Q 2B , Q 3A , Q 3B , Q 4A , Q 4B , Q 5A , Q 5B , Q 5C , Q 7 , Q 8 and Q B are independently for each occurrence absent, alkylene, substituted alkylene wherein one or more methylenes can be interrupted or terminated by one or more of O, S, S(O), SO 2 , N(R N ), C(R′)═C(R″), C≡C or C(O); T B and T B′ are each independently for each occurrence absent, CO, NH, O, S, OC(O), OC(O)O, NHC(O), NHC(O)NH, NHC(O)O, CH 2 , CH 2 NH or CH 2 O; R x is a lipophile, or a cationic lipid; R 1 , R 2 , R 2A , R 2B , R 3A , R 3B , R 4A , R 4B , R 5A , R 5B , R 5C , R 7 are each independently for each occurrence absent, NH, O, S, CH 2 , C(O)O, C(O)NH, NHCH(R a )C(O), —C(O)—CH(R a )—NH—, CO, CH═N—O, or heterocyclyl; L 1 , L 2A , L 2B , L 3A , L 3B , L 4A , L 4B , L 5A , L 5B and L 5C are each independently for each occurrence a carbohydrate; R′ and R″ are each independently H, C 1 -C 6 alkyl, OH, SH or N(R N ) 2 ; R N is independently for each occurrence methyl, ethyl, propyl, isopropyl, butyl or benzyl; R a is H or amino acid side chain; Z′, Z″, Z′″ and Z′″ are each independently for each occurrence O or S; p represent independently for each occurrence 0-20.