【摘要】 胰島素B鏈中C-端十肽的衍生物,即cbz·（γ-OCH₃）glu·（N^G-NO₂）arg·gly·phe·phe·tyr·thr·pro·（ε-Tos）lys·ala·OCH₃(B_21-30)曾从cbz·（γ-OCH₃）glu·（No-NO₂）arg·OH(B_21-22a)和H·gly·phe·phe·tyr·thr·pro·（ε-Tos）lys·ala·OCH₃(B_23-30b)用碳二亚胺法于DMF中縮合而得。其中B_23-30b由cbz·gly·phe·phe·tyr·thr·pro·（ε-Tos）lys·ala·OCH₃(B_23-30)經催化氫化而得,B_21-22a系由cbz·（γ-OCH₃）glu·ONP和硝基精氨酸縮合而成。B_21-30經皂化所得的保护的十肽,cbz·glu·（N^G-NO₂）arg·gly·phe·phe·tyr·thr·pro·（ε-Tos）lys·ala·OH(B_21-30a),能为腎羧肽酶所全部水解,而为胰羧肽酶消化时只释放出C-端的丙氨酸,这与N-苄氧羰基八肽(B_23-30a)或胰島素链經同样处理所得的結果相符。B_21-30a經較長时間的催化氫化可以脫除N^α-的苄氧羰基和N^G-的硝基,获得N^ε-对甲苯磺酰化的自由十肽,但用B_21-30在同样条件下进行催化氫化所释放出的α-氨基很容易消失,估計它和γ-甲酯縮合,形成四氫吡咯酮?木烹难苌铩T谖⑺嵝匀芤褐杏?0℃的长时期的暴露,短时期的热水浴的处理或在微碱性溶液中进行层析的放置,均能促使此种环化。任何胍基已游离的十肽衍生物,不論其中的α-氨基已否环化,均能定量地被胰蛋白酶水解成八肽和二肽的衍生物,因而肯定了十肽的光学純度。更多还原

【Abstract】 Carbobenzoxy-γ-methylglutamylnitroarginylglycylphenylalanylphenylalanyltyrosylthreonylprolyl（ε-tosyl）lysylalanine methyl ester (B_21-30), a derivative of the C-terminal decapeptide of the B-chain of insulin, has been prepared by coupling carbobenzoxy-γ-methylglutamylnitroarginine with glycylphenylalanylphenylalanyltyrosylthreonylprolyl（ε-tosyl）lysylalanine methyl ester by the carbodiimide method. The dipeptide derivative has been prepared by condensing nitroarginine with p-nitrophenyl carbobenzoxy-γ-methyl glutamate while the octapeptide ester has been obtained from carbobenzoxyoctapeptide methyl ester by catalytic hydrogenolysis. Saponification of the protected decapeptide ester gave rise to carbobenzoxyglutamylnitroarginylglycylphenylalanyl phenylalanyltyrosylthreonylprolyl （ε-tosyl）lysylalanine (B_21-30) which could be completely digested by kidney carboxypeptidase. The finding that only alanine was liberated from the protected decapeptide by the action of pancreatic carboxypeptidase, in accord with the results of the synthetic protected octapeptide as well as the B-chain of insulin, further proved the homogeneity of the product. N^?-tosylated free decapeptide could be obtained from the protected decapeptide (B_21-30a) by prolonged catalytic hydrogenolysis while upon the same treatment on the protected decapeptide ester was isolated the decapeptide ester as well as some of its cyclized product which was presumably resulted from the former by condensation of the α-amino with the γ-methyl ester group. The readiness of such cyclization into pyrollidone derivative could be greatly enhanced by prolonged standing at 30℃ in slightly acidic medium, brief heating of the aqueous solution or during the chromatography with ammoniabutanol solvent system.All decapeptide derivatives despite the presence or absence of α-amino but with free guanidino group could be completely hydrolyzed by trypsin into di- and octa-peptide derivatives. This finding further verified the optical purity of the decapeptide.更多还原