CHEMICAL PATHWAYS OF PEPTIDE DEGRADATION .3. EFFECT OF PRIMARY SEQUENCE ON THE PATHWAYS OF DEAMIDATION OF ASPARAGINYL RESIDUES IN HEXAPEPTIDES
CHEMICAL PATHWAYS OF PEPTIDE DEGRADATION .3. EFFECT OF PRIMARY SEQUENCE ON THE PATHWAYS OF DEAMIDATION OF ASPARAGINYL RESIDUES IN HEXAPEPTIDES
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DOI：
10.1023/a:1015999012852
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发表时间：
1990-08-01
影响因子：
3.7
通讯作者：
BORCHARDT, RT
中科院分区：
文献类型：
--
作者：
PATEL, K;BORCHARDT, RT
Asn残基的脱酰胺可以通过Asn残基的直接水解或通过环状酰亚胺中间体发生。采用在Asn残基的C-末端侧（Y）和N-末端侧（X）具有取代的Val-Tyr-X-Asn-Y-Ala六肽，研究了一级序列对Asn残基脱酰胺途径的影响。在酸性介质中，肽通过直接水解Asn残基脱酰胺，仅产生Asp肽，而在中性或碱性条件下，肽通过形成环状酰亚胺中间体脱酰胺，环状酰亚胺中间体水解产生isoAsp和Asp肽。在中性至碱性pH下，脱酰胺速率受Asn残基C-末端侧氨基酸大小的显著影响。Asn残基C-末端一侧的氨基酸在酸性pH下对脱酰胺速率没有影响。Asn残基N-末端一侧的氨基酸结构的变化在所有研究的pH下对脱酰胺速率没有显著影响。对于缓慢脱酰胺的肽，还观察到涉及Asn侧链攻击肽羰基碳导致肽键断裂的反应。
Deamidation of Asn residues can occur either by direct hydrolysis of the Asn residue or via a cyclic imide intermediate. The effects of primary sequence on the pathways of deamidation of Asn residues were studied using Val-Tyr-X-Asn-Y-Ala hexapeptides with substitution on the C-terminal side (Y) and on the N-terminal side (X) of the Asn residue. In acidic media the peptides deamidate by direct hydrolysis of the Asn residue to yield only Asp peptides, whereas under neutral or alkaline conditions, the peptides deamidate by formation of the cyclic imide intermediates which hydrolyze to yield both isoAsp and Asp peptides. At neutral to alkaline pH''s the rate of deamidation was significantly affected by the size of the amino acid on the C-terminal side of the Asn residue. The amino acid on the C-terminal side of the Asn residue has no effect on the rate of deamidation at acidic pH. Changes in the structure of the amino acid on the N-terminal side of the Asn residue had no significant effect on the rate of deamidation at all the pH''s studied. For peptides that underwent deamidation slowly, a reaction involving the attack of the Asn side chain on the peptide carbonyl carbon resulting in peptide bond cleavage was also observed.