bluuebunny/crossref_metadata_2025 huggingface dataset:
Conformation of the eosinophil chemotactic tetrapeptides and analogues in dimethyl sulfoxide.
Authors: BEILHARZ GEORG R. , SMITH JOHN A. , AUSTEN K. FRANK , WRIGHT PETER E.
Published: August 2010

Proton nuclear magnetic resonance parameters are reported for DMSO‐d6 solutions of the eosinophil chemotactic tetrapeptides, Val1‐Gly2‐Ser3‐Glu4and Ala1‐Gly2‐Ser3‐Glu4, as well as three analogues of the Val1tetrapeptide, d‐Val1, Ala2and Ala3. The synthesis of Val‐(S)‐[α‐2H1] Gly‐Ala‐Glu, in which the glycine has been stereospecifically deuterated in the Hα3position, has allowed the assignment of the 1H resonances belonging to individual Hα2and Hα3glycine methylene protons. Simulation of the glycine ABX spin system yields two vicinal coupling constants which are consistent with a highly preferred conformation about the glycine HN‐Cαbond. The chemical shifts, coupling constants, temperature coefficients of amide proton chemical shifts and calculated side chain rotamer populations are reported for all peptides, The coupling constant analysis and temperature coefficients of amide proton chemical shifts together suggest that a type I β‐turn conformation is preferred by the Ala3analogue. The 1H n.m.r. parameters of the other peptides suggest that these can also adopt a β‐turn conformation in DMSO. There are. however, considerable differences in the extent of conformational averaging undergone by the various peptides.
Structural changes of the 11 S globulin from sunflower seed (Helianthus annuus L.) after succinylation*
Authors: SCHWENKE KLAUS DIETER , RAUSCHAL EIKE , ZIRWER DIETRICH , LINOW KARL‐JOACHIM
Published: August 2010

The influence of various levels of succinylation on the structure of the 11 S globulin from sunflower seed has been studied by the techniques of sedimentation velocity, viscometry and by circular dichroism spectroscopy in the near and far ultraviolet region. The protein dissociates gradually with increasing degree of succinylation forming 7 S and 5 S intermediates. At a level of 70% succinylation a 2.5 S component occurs as the final product of dissociation. The intrinsic viscosity of the protein does not change remarkably until a succinylation of about 70%, where a drastic viscosity increase is observed. At this level of modification a decrease of the positive circular dichroism bands in the near ultraviolet region takes place. Contrary to this, the negative ellipticity of the far ultraviolet region increases at a high level of modification, suggesting an enhancement of the amount of helix conformation.
Cellobiohydrolase from Trichoderma reesei.
Authors: BHIKHABHAI RAMAGAURI , JOHANSSON GUNNAR , PETTERSSON GÖRAN
Published: August 2010

The secondary structure pattern of a cellobiohydrolase from Trichoderma reesei was predicted using three different algorithms. The relative amounts of the different secondary structure classes derived by this procedure were in good agreement with the values determined by circular dichroism measurements. A twofold internal sequence homology with a repeat distance of approximately 200 residues is observed and possibly also a third, partial, repetition in the C‐terminal region. The predicted secondary structure and hydrophobicity pattern show a similar repeat.
Primary structure of fin whale prolactin
Authors: TSUBOKAWA MAKOTO , MURAMOTO KOJI , KAWAUCHI HIROSHI
Published: August 2010

The primary structure of prolactin from fin whale pituitary has been elucidated. It consists of 199 amino acid residues with three disulfide bridges formed by residues 6–11, 58–174 and 191–199. The fin whale prolactin is highly homologous with other mammalian prolactins, especially with the porcine hormone.
Synthesis and opioid activity of partial retro‐inverso analogs of dermorphin
Authors: SALVADORI SEVERO , MARASTONI MAURO , BALBONI GIANFRANCO , SARTO GIANPIETRO , TOMATIS ROBERTO
Published: August 2010

We studied the effect of partial retro‐inverso modification of selected peptide bonds of dermorphin (H‐Tyr‐d‐Ala‐Phe‐Gly‐Tyr‐Pro‐Ser‐NH2. The modifications concern two consecutive peptide bonds (Phe3‐Cly4‐Tyr5, I) or a single one (Gly4‐Tyr5‐, II or Phe3‐Gly4, III). All pseudoheptapeptides showed low opioid activity in the in vitro and in vivo tests. Compound III has a biological potency comparable to that of morphine but only 2–5% of original dermorphin when tested in guinea pig ileum preparation and in mice tail‐flick assay after intra‐cerebro or subcutaneous administration.
Protection of the hydroxyl function of hydroxyproline and serine in peptide synthesis by the 2‐methoxyethoxymethyl (Mem) group
Authors: VADOLAS D. , GERMANN H.P. , THAKUR S. , KELLER W. , HEIDEMANN E.
Published: August 2010

Some tri‐ and hexapeptides containing hydroxyproline and serine were synthesized using the 2‐methoxyethoxymethyl group for the protection of the hydroxyl function. For N‐protection not only the NpS and the Z group but also the Boc group can be used. As compared to the But group the Mem group is much more stable towards TFA. Application of Mem protection allows a complete deblocking of the Boc group without affecting the Mem group.
Synthesis of protected peptides with the sequence 8–13‐1‐3 and 4–13‐1‐3 of mycobacillin and their analogs
Authors: MLADENOVA‐ORLINOVA L.V. , PETRICHEVA E.M.
Published: August 2010

We have synthesized both a protected nonapeptide of the mycobacillin 8–13‐1‐3 amino acid sequence and a protected tridecapeptide of the 4–13‐1‐3 sequence, which are a fragment and a open chain analog of this antibiotic, respectively. Some of their analogs with a reversed configuration of the amino acids at fixed positions have also been synthesized. The nonapeptides were obtained by coupling partially protected mycobacillin fragments with the sequence 8–10 and 11–13‐1‐3 while the tridecapeptides were synthesized by coupling partially protected fragments 4–7 and 8–13‐1‐3. Configuration analogs of these fragments were also used. The coupling methods applied were DCCI/HONSu or DCCI/HOBt. The purification of the synthesized peptides was achieved by means of recrystallization or column chromatography on silica gel. They were characterized mainly by m.p., degree of optical rotation, elemental and amino acid analysis.
SMS 201–995, a very potent analogue of somatostatin. Assignment of the1H 500 MHz n.m.r. spectra and conformational analysis in aqueous solution
Authors: WYNANTS C. , van BINST G. , LOOSLI H.R.
Published: August 2010

The conformations of a cyclic analogue of somatostatin, SMS 201–995, have been studied by n.m.r. spectroscopy at 500 MHz in aqueous solution. Assignments were made by use of 2D‐correlated methods, especially by detecting long‐range connectivities in order to identify the aromic amino‐acid and long‐range couplings between α protons of consecutive residues. Measurements of temperature coefficients of amide protons and of NH‐CαH coupling constants enabled us to conclude that in water the molecule is rather flexible, with no evidence for a β turn structure involving Thr6. An equilibrium involving two γ turn conformations stabilized respectively by Cys2‐d‐Trp4and Phe3‐Lys5hydrogen bonds, is responsible for the large upfield shift observed for the Lys5γ protons and is compatible with the measured JNH‐CαHcoupling constants.
Conformations of peptides containing 1‐aminocyclohexanecarboxylic acid (Acc6). Crystal structures of two model peptides
Authors: BARDI R. , PIAZZESI A.M. , TONIOLO C. , SUKUMAR M. , RAJ P. ANTONY , BALARAM P.
Published: August 2010

The crystal structures of two peptides containing 1‐aminocyclohexanecarboxylic acid (Acc6) are described. Boc‐Aib‐Acc6‐NHMe · H2O adopts a β‐turn conformation in the solid state, stabilized by an intramolecular 4 → 1 hydrogen bond between the Boc CO and methylamide NH groups. The backbone conformational angles (φAib = – 50.3°, ψAib = – 45.8°; φAcc6 = – 68.4°, ψAcc6 = – 15°) lie in between the values expected for ideal Type I or III β‐turns. In Boc‐Aib‐Acc6‐OMe, the Aib residue adopts a partially extended conformation (φAib = – 62.2°, ψAib = 143°) while the Acc6residue maintains a helical conformation (φAcc6 = 48°, ψAcc6= 42.6°). 1H n.m.r. studies in CDCl3 and (CD3)2SO suggest that Boc‐Aib‐Acc6‐NHMe maintains the β‐turn conformation in solution.
1‐Deoxyglycitolation of protein amino groups and their regeneration by periodate oxidation*
Authors: WONG W.S. DOMINIC , KRISTJANSSON MAGNUS M. , OSUGA DAVID T. , FEENEY ROBERT E.
Published: August 2010

Reductive alkylation of lysyl e‐amino groups with sugars (1‐deoxyglycitolation) using pyridine borane as the reducing agent has been recently described [Wong, W.S.D., Osuga, D.T. & Feeney, R.E. (1984) Anal. Biochem.139, 58–67]. The regeneration of the lysines has now been achieved by oxidation with e10 mM periodate. In experiments with glycitolated bovine serum albumin, reactions using 5, 20, and 80 mM periodate were essentially complete in the first 10 min. Oxidations of methionine to the sulfoxide were evident even at this lower concentration of periodate, while higher concentrations and prolonged reaction times only caused unnecessary destruction of amino acids. The removal was shown to occur in a wide pH range with little variation in the recovery of the lysines. The degree of glycitolation, or the nature of the attached carbohydrate residues, had no effect on the yield of products. Reductive 1‐deoxygalactitolation of e55% of the lysyl e‐amino groups of lysozyme caused no loss in enzymatic activity; when 5 mM periodate was used to remove the 1‐deoxy‐galactitol moiety, e95% of the amino groups were regenerated, concomitant with destruction of e16% of the activity. On reductive 1‐deoxygalactitolation of the amino groups of turkey ovomucoid, 65% of the lysyl e‐amino groups were modified with 70% loss of the inhibitory activity against trypsin. On treatment with 5 mM periodate, e80% of the amino groups were regained with a similar recovery of the inhibitory activity.
Single chain des‐(B30) insulin
Authors: MARKUSSEN JAN , JØRGENSEN KLAVS H. , SØRENSEN ANDERS R. , THIM LARS
Published: August 2010

Single chain des‐(B30) insulin (SCI) has been synthesized from porcine insulin by trypsin in a medium with a low content of water. Trypsin catalyzes an intramolecular transpeptidation reaction in which the glycineA1 residue substitutes the alanineB30 residue, rendering a LysB29‐GlyA1 peptide link between the A‐and B‐chains of insulin. The insulin derivative has been purified by column chromatography and appears to be homogeneous in HPLC and disc electrophoresis. The structure was proven to be B(1–29)–A(1–21) insulin by proteolysis with Armilliaria mellea protease followed by a few steps of Edman degradation. The electrophoretic mobility indicates that SCI has a more condensed structure than that of insulin. Perfect rhombohedral crystals were obtained under conditions resembling those under which insulin crystallizes in the same form. SCI was devoid of effect in the blood sugar lowering assay in mice, the estimated potency being less than 0.1% of that of insulin.
N‐methylamino acids in peptide synthesis
Authors: STEINAUER RENE , CHEN FRANCIS M.F. , BENOITON N. LEO
Published: August 2010

The mixture of N‐alkoxycarbonyl‐ or N‐acylamino acid substrate and corresponding N‐methylated product is analyzed by HPLC on a μBondapak‐C18 column with acidic aqueous methanol as eluent and u.v.‐absorbance monitoring.
N‐Acyl‐diketopiperazines
Authors: ANNACALCAGNI  , MAZZA FERNANDO , POCHETTI GIORGIO , ROSSI DOMENICO , LUCENTE GINO
Published: August 2010

As shown by the values of dCα (0.487 and 0.442 ÅA) and by the β angle of folding (41°), N‐(pyruvoyl)‐cyclo(‐L‐Phe‐D‐Pro‐) (I) in the crystals adopts a boat conformation whose high degree of buckling approaches the values found in proline containing homochiral diketopiperazines. Only one peptide bond is slightly non planar with ω2= ‐4.7°. The imide ‐CO‐N‐CO‐ group is practically planar and not conjugated with the ketonic carbonyl; the angle between the planes containing the two groups being 79.7°. The proline ring is in a β‐envelope conformation. The axial benzylic side chain of the Phe residue in the crystal adopts an unexpected extended conformation (X11= ‐60.9°) which is not retained in chloroform solution, where the folded conformation is preferred. Crystals: space group P21 with a = 9.039(7), b = 14.472(6), c = 6.215(6)ÅA, β= 106.24(6)° and Z = 2. The final R and Rw are 0.049 and 0.068, respectively.
Preparation of photoreactive derivatives of trypsin‐chymotrypsin inhibitors from soybeans and chick peas by selective modification of lysine residues
Authors: SMIRNOFF PATRICIA , RAMACHANDRAN J. , BIRK YEHUDITH
Published: August 2010

Photoreactive derivatives of the Bowman‐Birk trypsin‐chymotrypsin inhibitor (BBI) from soybeans and of CI, the trypsin‐chymotrypsin inhibitor from chick peas, were prepared by selective modification of the e‐amino groups of lysine residues with 2‐nitro‐4(5)‐azidophenylsulfenyl chlorides (2,4(5)‐NAPS‐C1). The ultraviolet absorption spectra of the photolabeled inhibitors indicated that three out of the five lysines of BBI and one of the seven lysines of CI were modified. The inhibitory activity of the modified inhibitors towards trypsin and chymotrypsin was not reduced even after photolysis. The specific lysine residues that constitute the trypsin‐inhibitory sites of BBI and CI did not react with the photoreactive reagents. Further modification of the photoreactive derivatives of BBI and CI with maleic anhydride, directed towards the trypsin‐reactive sites, resulted in almost complete loss of the trypsin‐inhibiting activity without reducing the ability to inhibit chymotrypsin. A pronounced potentiation effect (e 2x) of the chymotrypsin inhibiting activity was noted for 2,5‐NAPS‐CI and it was retained even after maleylation followed by photolysis, raising the possibility of exposure of an additional chymotrypsin inhibitory site in CI.
The antibiotic edeine
Authors: WOJCIECHOWSKA HANNA , KONITZ ANTONI , BOROWSKI EDWARD
Published: August 2010

Edeine D is pentapeptide amide produced with other edeines by Bacillus brevis Vm4 strain. This antibiotic is composed of glycine (Gly), isoserine (Ise), 2,3‐diaminopropionic acid (A2pr), 2,6‐diamino‐7‐hydroxyazelaic acid (A2ha), 3‐amino‐3‐phenyl‐propionic acid (Iph), and spermidine (Spe). Partial and full acid hydrolysis, enzymatic degradation with carboxypeptidase B, periodate‐permanganate oxidation and examination of Dnp‐derivatives suggested the following structure of edeine D: (S)‐Iph‐(S)‐Ise‐(S)‐A2 pr‐(R,S,R)‐A2 ha‐(Gly‐Spe).
Synthesis of Z‐CCK‐27–32‐NH2, Z‐Tyr(So3‐)‐Met‐Gly‐Trp‐Met‐Asp‐NH2, a cholecystokinin receptor antagonist and an inhibitor of gastrin‐induced acid secretion
Authors: BRIET CHRISTIAN , AUMELAS ANDRÉ , MARTINEZ JEAN
Published: August 2010

The synthesis of the hexapeptide Z‐Tyr(SO3‐)‐Met‐Gly‐Trp‐Met‐Asp‐NH2, representing the C‐terminal sequence of cholecystokinin minus the C‐terminal phenylalanyl residue is described. This peptide was shown to be the most potent cholecystokinin receptor antagonist in vitro described to date. It is also able to inhibit gastrin‐induced acid secretion in vivo, in the rat and was proved to antagonize the action of the C‐terminal octapeptide of cholecystokinin in the central nervous system.
Chemical synthesis of insulin‐like growth factor II
Authors: YAMASHIRO DONALD , LI CHOH HAO
Published: August 2010

Human insulin‐like growth factor II (IGF‐II) with 67 amino acids and three disulfide bridges has been synthesized by the solid‐phase method. The synthetic hormone is shown to be homogeneous in high performance liquid chromatography (HPLC), high performance partition chromatography (HPPC), and chromatofocusing. It is indistinguishable from natural hormone in HPLC, peptide map of thermolysin digests, amino acid composition and radioreceptor binding assay. Thus, synthetic and natural IGF‐II are identical.
X‐ray studies on crystalline complexes involving amino acids and peptides
Authors: SURESH C.G. , VIJAYAN M.
Published: August 2010

The hexahydrate of a 1:1 complex between L‐histidyl‐L‐serine and glycyl‐L‐glutamic acid crystallizes in space group P1 with a = 4.706(1), b= 8.578(2), c= 16.521(3) ÅA; α= 85.9(1), β= 89.7(1)°, n̈= 77.4(1). The crystal structure, solved by direct methods, has been refined to an R value of 0.046 for 2150 observed reflections. The two peptide molecules in the structure have somewhat extended conformations. The unlike molecules aggregate into separate alternating layers. Each layer is stabilized by hydrogen bonded head‐to‐tail sequences as well as sequences of hydrogen bonds involving peptide groups. The arrangement of molecules in each layer is similar to one of the plausible idealized arrangements of L‐alanyl‐L‐alanine worked out from simple geometrical considerations. Adjacent layers in the structure are held together by interactions involving side chains as well as water molecules. The water structure observed in the complex provides a good model, at atomic resolution, for that in protein crystals. An interesting feature of the crystal structure is the existence of two water channels in the interfaces between adjacent peptide layers.
Evidence for the steric proximity of Tyr 174 and Lys 111 in bovine growth hormone
Authors: NOWICKI C. , WOLFENSTEIN‐TODEL C. , SANTOME J.A.
Published: August 2010

Bovine growth hormone was modified by reaction with 1,5‐difluoro‐2,4‐dinitro‐benzene under conditions favouring production of intramolecularly crosslinked derivatives from monomeric molecules. The monomeric fraction, isolated by chromatography on Sephadex G‐100, was oxidized or reduced and carbamido‐methylated and trypsin digested. The resulting peptides were fractionated on SP‐Sephadex and further purified by peptide mapping or HPLC. Two modified peptides containing sequences 108–112 or 108–113 and 171–176 of bGH were obtained, including a dinitrophenylene bridge between lysine 111 and tyrosine 174, thus suggesting the stereochemical proximity of these residues.
Complete covalent structure of a proline‐rich phosphoprotein, PRP‐2, an inhibitor of calcium phosphate crystal growth from human parotid saliva
Authors: SCHLESINGER DAVID H. , HAY DONALD I.
Published: August 2010

Human salivary secretions contain many proteins in which proline forms an unusually large fraction of the amino‐acid residues present, typically from 20% to over 40% (1,2). These proteins are also unusually rich in glycine and glutamine, generally account for over half the total protein in saliva, and include acidic (3,4), basic (5–7) and glycosylated (8) molecules. The functions of most of these are not clearly defined. One group, however, the acidic proline‐rich phosphoproteins (PRP), have been shown to be potent inhibitors of secondary precipitation (crystal growth) of calcium phosphate salts (9–11). Acting together with a salivary protein inhibitor of primary precipitation of calcium phosphates, statherin (12), the PRP stabilize saliva which is supersaturated with respect to the calcium phosphate salts which form dental enamel (13). These inhibitory activities act to provide a protective, reparative, but stable environment for dental enamel, which is important for maintaining the health of the teeth (14). The PRP are a complex group of phosphoproteins which include four major (3) and at least eight minor members (15). The primary structures of three of the major proteins have been determined. These are PRP‐1, also designated Protein‐C (16), PRP‐3, also designated Protein‐A (17), and PRP‐4 (18). The designations PRP‐1,‐2,‐3 and ‐4 (3) will be used here. The purpose of this paper is to report the complete primary structure of PRP‐2 as a further step towards establishing the structural basis of the biological activity of the PRP, and clarifying the genetic and biosynthetic relationships of these closely related proteins.
Synthesis of N3‐fumaramoyl‐L‐2,3‐diaminopropanoic acid analogues, the irreversible inhibitors of glucosamine synthetase
Authors: ANDRUSZKIEWICZ RYSZARD , CHMARA HENRYK , MILEWSKI SLAWOMIR , BOROWSKI EDWARD
Published: August 2010

Several analogues of N3‐fumaramoyl‐L‐2,3‐diaminopropanoic acid were synthesized and evaluated for inhibition of glucosamine‐6‐phosphate synthetase activity. The syntheses were accomplished by acylation reaction of N2‐tert.‐butoxycarbonyl‐L‐2,3‐diaminopropanoic acid (Boc‐A2pr) or N2‐tert.‐butoxy‐carbonyl‐L‐2,4‐diaminobutanoic acid (Boc‐A2‐bu) with the N‐succinimidoyl esters of several derivatives of α, β‐unsaturated acids 2a‐d followed by deprotection of the Boc groups. The obtained compounds were tested for inhibition of glucosamine synthetase isolated from Salmonella typhimurium and Saccharomyces cerevisiae. The results indicated that among the synthesized compounds, N3‐4‐methoxyfumaroyl‐L‐2,3‐diaminopropanoic acid (FMDP) was the most powerful inhibitor of glucosamine synthetase.
Structure and conformation of linear peptides VII.
Authors: LALITHA V. , MURALI R. , SUBRAMANIAN E.
Published: August 2010

The tripeptide, L‐valyl‐glycyl‐glycine (C9H17N3O4, molecular weight = 231), crystallizes in the monoclinic space group C2, with a = 24.058(3)Å, b = 4.801(1), c = 10.623(2), β = 110.02(1)° and Z = 4. The structure was determined by direct methods and refined to a final R‐index of 0.043 for 830 reflections (sinθ/Λ ≤ 0.53 A‐1) with I> 1.0s̀. The molecule exists as a zwitterion. The peptide units are trans and one of them shows significant deviations from planarity (Δω2 = 9.3°). The peptide chain repeat distance, 1Cα‐3Cα, is 7.23Å and the molecule displays a highly extended conformation with backbone torsion angles of ψ1 = 123.1°, ω1 = ‐ 179.4°, ø2 = ‐ 155.1°, ψ;2 = 154.7°, ω2 = 170.7°, ø3 = ‐ 146.6° and ψ3 = 180.0°. For the valyl side chain, χ11 = ‐ 52.5°, χ12 = 174.2°. The packing involves hydrogen‐bonded interactions between successive molecules related by the β‐translation of the lattice, giving rise to the familiar parallel β‐sheet structure which appears to be the most extended one observed to date.
Structure and conformation of linear peptides
Authors: MURALI R. , SUBRAMANIAN E. , PARTHASARATHY R.
Published: August 2010

The crystal structure of t‐Boc‐glycyl‐L‐phenylalanine (C14H22N2O5, molecular weight = 298) has been determined. Crystals are monoclinic, space group P21, with a = 7.599(1)Å, b = 9.576(2), c = 12.841(2), β = 97.21(1)°, Z = 2, Dm = 1.149, D° = 1.168 g · cm‐3. Trial structure was obtained by direct methods and refined to a final R‐index of 0.064 for 1465 reflections with I> 1s̀. The peptide unit is trans planar and is nearly perpendicular to the plane containing the urethane moiety. The plane of the carboxyl group makes a dihedral angle of 16.0° with the peptide unit. The backbone torison angles are ω0 = ‐ 176.9°, ø1 = ‐ 88.0°, ψ1 = ‐ 14.5°, ω1 = 176.4°, ø2 = ‐ 164.7° and ψ2 = 170.3°. The phenylalanine side chain conformation is represented by the torsion angles χ1 = 52.0°, χ2 = 85.8°.
Chemical synthesis and immunological properties of a cyclic eicosapeptide (Gly88,90) 82–101 of the beta subunit of human chorionic gonadotrophin
Authors: IYER K.S.N. , SAHAL D. , TALWAR G.P.
Published: August 2010

The eicosapeptide (Gly88,90) 82–101 hCG‐β was synthesized by the fragment condensation of the nonapeptide (Gly88,90) 82–90 and the undecapeptide 91–101 followed by iodine oxidation to make the disulfide loop. Intramolecularity of the disulfide linking cysteines at 93 and 100 was confirmed. Anti‐peptide antibodies were elicited in rabbits upon immunization with a conjugate of the peptide with tetanus toxoid. The repertoire of these antibodies was directed solely against the undecapeptide 91–101. These antibodies showed no recognition for hCG, hCG‐β or ARCM hCG‐β, suggesting that the conformational epitopes of hCG‐β in the region 82–101 may not be accessible to antibodies.
Oxytocin analogs with oxygen‐containing side chains in position 3
Authors: GAZIS DIANA , SCHWARTZ IRVING L. , CORDOPATIS PAUL , THEODOROPOULOS DIMITRIOS
Published: August 2010

We have synthesized three oxytocin analogs containing an oxygen atom in the amino acid side chain in position 3 to determine the influences of increased side chain length and of hydrophilicity on the potencies and specificities of the resulting analogs. These three analogs: – [3‐O‐methylhomoserine] oxytocin, [3‐O‐ethylserine] oxytocin, and [3‐O‐methylthreonine] oxytocin – have the following activities in U/mg: 490, 208, 265, milk ejection; 125, 129, 63, uterusin vivo; 0.2, 16, 0.03, antidiuretic; and 0.1, 0.5, 0.1, pressor. The results show that a longer side chain, [3‐O‐methylhomoserine] and [3‐O‐ethylserine] vs. [3‐O‐methylthreonine], tends to increase all activities. Moving the hydrophilic oxygen farther away from the peptide backbone, on the other hand, decreases vasopressin‐like activities but increases or has no effect on oxytocin‐like activities.
Comparative biological activities of potent analogues of α‐melanotropin
Authors: WILKES BRIAN C. , CODY WAYNE L. , HRUBY VICTOR J. , CASTRUCCI ANA MARIE DE L. , HADLEY MAC E.
Published: August 2010

Several α‐melanotropin (α‐MSH) analogues with para substituted aromatic and nonaromatic amino acids in the 7‐position of the hormone were prepared and their melanotropic activities determined in the frog (Rana pipiens) and lizard (Anolis carolinensis) skin bioassays. D and L‐Phe(p‐NO2), D‐ and L‐Tyr, D‐ and L‐Ala, and Gly were substituted in the 7‐position. The use of substituted D or L‐aromatic amino acids in the 7th position of the central Ac‐[Nle4] ‐α‐MSH4–11 ‐ NH2 fragment resulted in a loss in potency relative to the corresponding phenylalanine‐containing analogue. The loss in potency cannot be due entirely to steric hindrance at the melanophore receptor, since nonaromatic amino acids substituted in the 7th position of this octapeptide fragment also generally led to a loss in biological activity. We reported previously that replacement of phenylalanine‐7 by its D enantiomer led to a marked increase in potency in each fragment analogue tested. Analogues containing other D amino acids in the 7th position also were more potent than their L amino acid‐containing analogues with one exception: Ac‐[Nle4, Ala7]‐α‐MSH4–11‐NH2 was more potent than Ac‐[Nle4, D‐Ala7]‐α‐MSH4–11‐NH2 in the frog skin bioassay. Replacement of phenylalanine‐7 by glycine resulted in a large decrease in potency in both bioassays, illustrating the importance of the side chain group, in this position of α‐MSH, to biological potency of the hormone.
Calcium binding cyclic hexapeptide
Authors: VARUGHESE K.I. , AIMOTO S. , KARTHA G.
Published: August 2010

The synthetic cyclic hexapeptide (L‐prolyl‐glycyl)3 forms a 2 : 1 complex with Ca2+ ion. The cation is sandwiched between the two peptide molecules. The gly‐cyl carbonyls from each of the peptides are octahedrally coordinated to the cation with an average calcium oxygen coordination distance of 2.26Å. Both the molecules coordinating to the calcium ion have three fold symmetry, but show significant conformational differences. In one of the peptides of the sandwich, the alternate carbonyls point to the opposite sides of the peptide ring while in the other, all the six carbonyls point to the same side of the ring. Three N‐H…O hydrogen bonds between the peptides add to the stability of the sandwich.
Cystamine‐enkephalin dimer
Authors: KONDO MICHIO , KODAMA HIROAKI , COSTA TOMMASO , SHIMOHIGASHI YASUYUKI
Published: August 2010

A cystamine‐enkephalin dimer, containing two molecules of [D‐Ala2, Leu5] enkephalin cross‐linked at theCOOH‐terminal leucine residue with cystamine, (NH2‐CH2‐CH2‐S‐)2, has been synthesized in order to examine directly the dimerization effect of an enkephalin molecule on the opiate receptor interactions. In a comparison of potencies against [3H]‐[D‐Ala2,D‐Leu5]enkephalin (3H‐DADLE) and [3H]‐[D‐Ala2,MePhe4,Gly‐ol5]enkephalin (3H‐DAGO) as delta and mu tracers, respectively, enkephalin dimer showed a very high affinity, especially for the delta opiate receptors. Dimer was almost threefold more potent than DADLE, which is one of the most utilized delta ligand to date. When the binding affinity of cystamine‐dimer was compared with that of its reduced thiol‐monomer, namely [D‐Ala2,Leu5, cysteamine6]enkephalin, the increment in affinity was four to fivefold for both delta and mu receptors. The results strongly indicate that the dimeric enkephalin is more potent presumably due to the simultaneous interaction with the two binding sites of the opiate receptors.
Structure and conformation of linear peptides
Authors: LALITHA V. , SUBRAMANINA E. , PARTHASARATHY R.
Published: August 2010

The tripeptide, L‐prolyl‐glycyl‐glycine, crystallizes in the trigonal space group P32, with a = b = 8.682(2)Å, c= 12.008(2) and Z = 3. The structure was solved by direct methods and refined to an R‐value of 0.07 for 727 reflections (I > 1.0s̀). The molecule exists as a zwitterion in the crystal. The peptide units and trans and show significant deviations from planarity (ω1 = 169.7o, ω2=‐170.1o). The peptide backbone adopts a left‐handed helical conformation similar to that of polyglycine II and polyproline II.
Solid‐phase synthesis of trypsin inhibitor CMTI III from squash seeds (Cucurbita maxima)*
Authors: KUPRYSZEWSKI GOTFRYD , RAGNARSSON ULF , ROLKA KRZYSZTOF , WILUSZ TADEUSZ
Published: August 2010

Using the solid‐phase procedure, a linear 29‐peptide with the reported sequence of trypsin inhibitor CMTI III was synthesized and oxidized to give three disulphide bridges. After affinity chromatography on an immobilized anhydrotrypsin column the synthetic product was shown by various physical techniques to be identical with the trypsin inhibitor CMTI III from squash seeds (Cucurbita maxima).
Circular dichroism investigations on the conformation of linear, cyclic and polymeric peptides containing His, Ser and Asp residues
Authors: NISHI NORIO , NAKAJIMA BUN‐ICHIRO , YONEYAMA MICHIO , TOKURA SEIICHI , AKIHIROTSUTSUMI
Published: August 2010

Conformational studies on the linear, cyclic and polymeric peptides with the sequences ‐Asp‐ßAla‐Gly‐Ser‐ßAla‐Gly‐His‐ßAla‐Gly‐(nonapeptide series) and ‐Asp‐eAhx‐Ser‐eAhx‐His‐eAhx (hexapeptide series) were carried out by means of circular dichroism measurements to clarify the relationship between their conformation and ester hydrolytic activity. It was suggested that all of the present peptides take a certain ordered conformation at acidic pH region and have a tendency to transform to a disordered conformation with a rise of pH. In the course of the conformational change, the linear and polymeric peptides undergo a drastic conformational change at around pH 7.0, while the cyclic peptides maintain the ordered conformation to some extent even at the basic pH region. Although this ordered conformation maintained in the cyclic peptides was estimated not to be a tight one, it was more stable in the cyclic peptide of the latter sequence (Cyclic‐6) than in the former sequence (Cyclic‐9). As reported previously, Cyclic‐6 showed greater activity than the others in the hydrolysis of various ester substrates. Higher activity and more stable ordered conformation of Cyclic‐6 seem to be closely related. The effects of urea, organic solvent, salt and change of temperature on their conformation are also reported.
Characterization of cleavage products in selected human lutropin preparations
Authors: Ward Darrell N. , Glenn Stephan D. , Nahm Hyun S. , Wen Ted
Published: August 2010

Low molecular weight fragments derived from the beta subunit of human lutropin have been frequently observed. These fragments are detected by polyacrylamide gel electrophoresis in sodium dodecyl sulfate following reduction of the disulfide bonds. A sample of human lutropin was identified that had a major portion of its beta subunit showing this proteolytic nick. Over 83% of the subunit was nicked based on reduction, carboxymethylation, and isolation of the low molecular weight fragments. This preparation had 53% of the activity of an intact human lutropin (radioligand assay). The proteolytic nick in the subunit was shown by N‐terminal sequencing of the C‐terminal fragments to be derived from three clips in a hexapeptide region (residues 44–49) characterized by hydrophobic alkyl side chains. Specific clips were on the amino side of Leu‐45 (8%), Val‐48 (45%) and Leu‐49 (47%). Thus the proteolytic activity, presumably derived from the pituitary during processing, has a substrate specificity reminiscent of the bacterial protease, thermolysin.
Glycolamidic ester group as labile linkage in solid phase peptide synthesis: use with FMOC‐protected amino acids
Authors: BALEUX FRANÇOISE , CALAS BERNARD , MERY JEAN
Published: August 2010

The glycolamidic ester (‐O‐CH2‐CO‐NH‐) was tested as labile linkage group in solid phase peptide synthesis using a polyacrylic resin and base‐cleavable fluor‐enylmethoxycarbonyl (FMOC) protecting group for α NH2. Although the glycolamidic ester group was known to be highly labile in basic conditions, the 32–36 thymopoietin segment, Arg‐Lys‐Asp‐Val‐Tyr (TP5), was obtained with high yield using a FMOC‐tBU strategy. The peptide was first deprotected on the carrier and then removed by saponification. The TP5 thus isolated was shown to be pure by high pressure liquid chromatography and amino acid analysis.
Structure‐function studies on human growth hormone
Authors: AUBERT MICHEL L. , BEWLEY THOMAS A. , GRUMBACH MELVIN M. , KAPLAN SELNA L. , LI CHOH H.
Published: August 2010

The relationship between the conformation of human pituitary growth hormone (hGH), biological activity, and ligand binding activity was studied by comparing conformational details previously published on in vivo and in vitro studies of identical samples of hGH and its known derivatives. In vivo assays included the rat tibia test for somatotropic activity and the pigeon crop‐sac assay for lactogenic hormone activity. Relative binding affinities were compared in radioimmuno‐assays using 125I‐hGH as tracer with 1) anti‐human chorionic somatomammotropin (hCS) serum (low discriminatory hybrid assay), 2) anti‐hGH sera (in conventional assays), 3) monospecific anti‐hGH serum (absence of cross‐reaction with hCS) and 4) human anti‐hGH sera obtained from GH‐deficient patients on replacement therapy. In addition, binding affinities were examined in two receptor‐binding assays, one specific for somatotropic activity (rabbit liver membranes, 125I‐hGH), and the other, for lactogenic hormones (rabbit mammary membranes, 125I‐oPRL). The conformational properties of native hGH and various chemically and enzymatically modified derivatives of the hormone were evaluated primarily from circular dichroism spectra, while conformational stabilities were estimated from the relative rates of tryptic digestion. Unfragmented, but chemically modified derivatives, exhibited good parallelism between retention or loss of native conformation and the in vivo potencies and in vitro binding affinities. None of the fragments of hGH showed activity in any of the radioreceptor assays or radioimmunoassays. Two derivatives of hGH, which contain gaps of 6 or 12 residues in the polypeptide backbone produced by partial enzymatic digestion, had full or increased in vivo potencies, full activities in the radioimmunoassays, and were the most active derivatives in both radio‐receptor assays. One of these, missing the hexapeptide corresponding to residues 135–140, was also found to retain nearly all the conformational properties of native hGH. These studies proved further evidence that 1) retention by modified forms of hGH of a high degree of in vivo biological potency or in vitro binding affinity is causally related to the retention of most of the conformation and conformational stability of the molecule, and 2) the biologically acitve, receptor‐binding and immunoreactive sites on the hGH molecule are 3‐dimensional in nature.
Preparation of Boc‐[S‐(3‐nitro‐2‐pyridinesulfenyl)]‐cysteine and its use for unsymmetrical disulfide bond formation
Authors: BERNATOWICZ MICHAEL S. , MATSUEDA REI , MATSUEDA GARY R.
Published: August 2010

The 3‐nitro‐2‐pyridinesulfenyl (Npys) derivative of cysteine was prepared and used to facilitate the formation of an unsymmetrical disulfide bond. Since this derivative is stable in trifluoroacetic acid:CH2Cl2 (1:1) and anhydrous hydrogen fluoride, Boc‐Cys(Npys) could be used directly in solid phase synthesis of the 14‐peptide acetyl‐Cys(Npys)‐Gly‐Glu‐Gln‐His‐His‐Pro‐Gly‐Gly‐Gly‐Ala‐Lys‐Gln‐Ala‐amide. Reaction of this peptide with the free thiol of another peptide, acetyl‐Gly‐Glu‐Gln‐His‐His‐Pro‐Gly‐Gly‐Gly‐Ala‐Lys‐Gln‐Cys‐amide, gave a single product containing an unsymmetrical disulfide bond. The amino acid composition of this product and HPLC analysis of its dithiothreitol reduction products were consistent with the desired heterodimer. As evidenced by HPLC, the mixed disulfide forms rapidly at alkaline pH and usefully over a wide pH range in aqueous buffers.
Multiple forms of pituitary prolactin, a glycosylated form of porcine prolactin with enhanced biological activity
Authors: PANKOV YU.A. , BUTNEV V.YU.
Published: August 2010

Three forms of prolactin differing in molecular weight (Mr 23 000, 25 000 and 50 000, respectively) and electrophoretic mobility have been isolated and purified from fresh‐frozen porcine pituitary glands. The prolactin form with Mr 25 000 is identified as a glycoprotein having an affinity to concanavalin A. The carbohydrate unit containing GlcN Ac3, GalNAc1, Man3, Fuc05, Gal04 is linked to asparagine at the 31 position. The amino acid composition and partial primary structure of the glycosylated prolactin are identical to those of the major prolactin form (Mr 23 000). Based on isoelectric focusing and non‐denaturing disc‐electrophoresis, the glycosylated prolactin appears more acidic than the major form. The glycosylated form of the hormone has 140% of the activity of the non‐glycosylated prolactin when measured by the pigeon crop sac assay. The new form accounts for 30–40% of the total monomeric prolactin in the porcine pituitary. The yield was 200 mg purified glycosylated prolactin from 1000g pituitary gland. The third form of hormone (Mr 50 000) was shown to be a disulphide linkéed prolactin dimer.
Primary structure of sperm whale luteinizing hormone
Authors: PANKOV YU.A. , KARASYOV V.S.
Published: August 2010

Luteinizing hormone was extracted from sperm whale pituitaries and separated into α‐ and β‐subunits. These subunits were cleaved with cyanogen bromide, and digested with trypsin and chymotrypsin. The fragments obtained were separated and purified by gel filtration on Sephadex and by ion exchange chromatography, reversed phase chromatography and chromatoelectrophoresis. The amino acid sequence of peptides obtained was studied by dansyl‐Edman's method and Edman's modification of Chang et al. The study made it possible to establish the complete amino acid sequence of sperm whale LHα‐ and β‐subunits.
Binding of 1‐anilinonaphthalene‐8‐sulfonic acid to type I collagen
Authors: Del POZO ALVARO MARTINEZ , OLMO NIEVES , ONADERRA MERCEDES , LIZARBE MARIA A. , GAVILANES JOSÉE G.
Published: August 2010

The existence of a hydrophobic cluster on the COOH‐telopeptides of type I collagen has been observed by studies on the binding of 1‐anilinonaphthalene‐8‐sulfonic acid (ANS) to this protein. Collagen contains one binding site for the fluorescent probe. This hydrophobic cluster remains after pepsin digestion thus indicating that it is formed by the undegraded portions of the COOH‐extrahelical ends of the protein. Energy transfer from tyrosine to ANS has been observed. The triple helix of collagen does not bind ANS.
Fluorogenic substrates for chymotrypsin with new fluorescent markers
Authors: KOKOTOS GEORGE , TZOUGRAKI CHRYSA
Published: August 2010

Several substrates for chymotrypsin Glt‐Phe‐NHRx have been synthesized, where RxNH2 are the compounds 3‐aminocoumarin (2), 6‐aminocoumarin (3), 3‐acetamido‐6‐aminocoumarin (4), 3‐acetamido‐8‐aminocoumarin (5), 7‐amino‐4‐methyl‐2‐quinolinone (AMQ), (6). The fluorescence properties of the new substrates and those of the corresponding free amines were examined. The compound 7‐glutarylphenylalaninamido‐4‐methyl‐2‐quinolinone (Glt‐Phe‐AMQ), (15), provided a new suitable substrate for chymotrypsin determination. The enzymatic release of the fluorophore AMQ was measured at Λex = 360nm and Λem=435nm. The Km of 15 was 0.5mM and its kcat/Km ratio was 47 M‐1 s‐1. By using this substrate, the detection limit of chymotrypsin was 10 ng/ml.
Quantitative description of side chain effects on binding to protein
Authors: CHARTON MARVIN
Published: August 2010

Values of ΔΔG previously reported for transition state binding of ATP and tyrosine by tyrosyl‐tRNA synthetase as a function of side chain structure are quantitatively described by the intermolecular force (IMF) equation. Polarizability, ionic side chains, and steric effects seem to be the major factors in determining ΔΔG. A contribution from hydrogen bonding cannot be excluded but is at best probably small. Binding is apparently due to dispersion forces and ion/dipole and ion‐induced/dipole interactions.
Dehydro‐dermorphins
Authors: SALVADORI SEVERO , MARASTONI MAURO , BALBONI GIANFRANCO , MARZOLA GIULIANO , TOMATIS ROBERTO
Published: August 2010

Dehydrophenylalanine having the Z‐configuration (ΔPhe) and D‐Phe were incorporated in positions 3 and/or 5 into dermorphin‐(1–5)‐peptide amide (H‐Tyr‐D‐Ala‐Phe‐Gly‐Tyr‐NH2) in order to study the effect of structure or configurational changes. On GPI preparation, whereas the activity of [L‐Phe5]‐pentapeptide was fourfold higher than parent peptide and comparable to that of dermorphin, the substitution of Phe3 by its D‐enantiomer was barely tolerated. The pentapeptides containing ΔPhe in positions 3 and/or 5 displayed even lower potency: particularly the unsaturation at position 3 alone or at position 3 and 5 was very detrimental to μ activity.
Synthesis and biological activity of carboxyl terminally extended dermorphins
Authors: MARASTONI MAURO , SALVADORI SEVERO , BALBONI GIANFRANCO , MARZOLA GIULIANO , DEGLIUBERTI ETTORE CIRO , TOMATIS ROBERTO
Published: August 2010

Dermorphinoyl(DMR)‐glycine, DMR‐sarcosine and DMR‐glycyl‐arginine have been prepared in order to examine the effect of C‐terminal extension of dermorphin (H‐Tyr‐D‐Ala‐Phe‐Gly‐Tyr‐Pro‐Ser‐NH2) on opioid activity.

On GPI preparation the addition of Gly, Sar, or Gly‐Arg to the carboxyl terminus of dermorphinoic acid was detrimental to μ activity: dermorphinoyl‐derivatives, in fact, retain only 5–20% of dermorphin potency.

Following intracerebroventricular administration (tail‐flick test), whereas the analgesic activities of compounds showed the trend dermorphin >DMR‐Sar> DMR‐Gly‐Arg>DMR‐Gly>morphine, the nonapeptide displayed highest activity after subcutaneous injection in mice: DMR‐Gly‐Arg was 2.5 and 10 times more potent than dermorphin and morphine, respectively.
Improved synthesis and purification of methylated amanitins using diazomethane*
Authors: LITTLE MICHAEL C. , PRESTON JAMES F. , BONETTI SANDRA
Published: August 2010

We have examined the conditions of methylating α‐amanitin with diazomethane with the intent of producing 6′‐O‐methyl‐α‐amanitin (meAMA). Under the appropriate conditions meAMA was afforded as the sole product in nearly quantitative yield. By exceeding the stoichiometries designed for optimal meAMA synthesis, a dimethylated amanitin, 1′‐N‐, 6′‐O‐dimethyl‐α‐amanitin (dimeAMA), was also produced. Both products were characterized, following HPLC, by ultraviolet and n.m.r. spectroscopy. Based upon their inhibitory potential against wheat germ RNA polymerase II, apparent dissociation constants of 4.3 nM and 5.4 nM were estimated for meAMA and dimeAMA, respectively.
Conformation and dynamics of the chemotactic peptide formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine in solution
Authors: VALENSIN GIANNI , LEPRI ANDREA , PASINI FRANCO LAGHI , ORRICO ALFREDO , CECCATELLI LINDA , CAPECCHI PIER LEOPOLDO , DI PERRI TULLIO
Published: August 2010

Several conformational and dynamic features of the chemotactic peptide formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine in solution have been delineated by investigations of NMR and IR spectroscopic parameters. Both 1D and 2D NMR experiments have been performed for detection of scalar and dipolar proton‐proton connectivities, whereas 13C and 1H relaxation parameters have been interpreted in terms of molecular dynamics. The main conformation appeared to be unfolded with the three hydrophobic side chains extending in divergent directions with respect to the backbone. The existence of relatively weak inter‐molecular hydrogen bonds was demonstrated, involving the formamide end group, with increase in the hydrophobicity of the external surface.
Synthesis of four diastereomeric enkephalins incorporating cyclopropyl phenylalanine
Authors: MAPELLI C. , KIMURA H. , STAMMER C.H.
Published: August 2010

Four diastereomeric D‐Ala2,Leu5‐enkephalins have been synthesized and their CD spectra and rat brain binding affinities determined. Only the peptides containing Z‐cyclopropyl phenylalanine residues showed strong binding affinity. No correlation between CD spectra and bioactivity could be made.
Variability in the backbone conformation of cyclic pentapeptides
Authors: KARLE ISABELLA L.
Published: August 2010

All the peptide bonds in cyclic(Gly‐LPro‐DPhe‐Gly‐LAla) are in the trans conformation; however, the peptide bond C5'‐N1 is twisted by 19° from planarity (ω5= ‐ 161°). A Type II β‐turn encompasses the LPro‐DPhe residues. Carbonyl oxygens O2, O4 and O5 are directed to the same side of the average plane through the backbone ring and they form hydrogen bonds with N3, N5 and N1, respectively, in adjacent molecules in a stacked column where the adjacent molecules are related by one translational unit. The conformation of the backbone is different from that established in other molecules with the DLDDL chirality sequence. The P21 cell contains two molecules of C21H26N5O5 with a = 4.836(2) A, b = 18.346(8) A, c = 12.464(5) A and β= 100.05(4)°. The R factor for 1382 data with ¶F0¶ > 1 ¶ is 7.0%.
Chemical synthesis of α‐inhibin‐92 by the thiocarboxyl segment coupling method
Authors: BLAKE JAMES , YAMASHIRO DONALD , RAMASHARMA K. , LI CHOH HAO
Published: August 2010

The 92 amino acid residue peptide, α‐inhibin‐92 (α‐IB‐92), has been synthesized by the thiocarboxyl segment strategy. Three segments were synthesized by the solid phase method, purified, and characterized: [GlyS34]‐α‐IB‐92‐(l‐34) (I), CF3CO‐[GlyS65]‐α‐IB‐92‐(35–65) (II), and Msc‐α‐IB‐92‐(66–92) (III). All were reacted with citraconic anhydride followed by removal of the Msc group in III to give Ia, IIa, and IIIa, respectively. Peptide IIIa was coupled to IIa by the silver nitrate/N‐hydroxysuccinimide procedure and, after removal of uncoupled segments and the trifluoroacetyl group, Ia was coupled followed again by removal of uncoupled segments. Final deblocking to remove citraconyl groups was accomplished under exceptionally mild conditions in aqueous acetic acid. The synthetic product was identical to natural α‐IB‐92 in amino acid analysis, HPLC, gel electrophoresis, and tryptic mapping. The synthetic peptide was indistinguishable from natural α‐IB‐92 in a radioimmunoassay and in an in vitro mouse pituitary assay for measuring suppression of FSH release in the presence of LHRH.
Semisynthesis of the native sequence of horse heart cytochrome c‐(66–104)‐nonatriacontapeptide
Authors: BOON P.J. , MOUS J.F.M. , TEN KORTENAAR P.B.W. , TESSER G.I.
Published: August 2010

The syntheses of some derivatives of horse cytochrome c‐(66–79)‐tetradeca‐peptide are presented. The syntheses are so designed that analogues of this phylogenetically well preserved sequence can be obtained also. The compounds were intended as synthons for the semisynthesis of 65‐homoserine‐cytochrome c, which we described earlier. A requisite for this project was the C‐terminal tetracosapeptide fragment of the protein, accessible through degradation of cytochrome c with cyanogen bromide. The five e amino groups in this compound are reversibly protected with the 2‐(methylsulfonyl)ethyloxycarbonyl function, which is resistant to acid and causes little impairment of solubility. The condensation of the fragments leading to the native sequence of horse cytochrome c‐(66–104)‐nonatriacontapeptide is presented also. The syntheses were performed using the solution strategy. Some unexpected ring closing reactions involving tyrosine and tert.‐butyl prolylasparaginylcarbazate, are described.