具有C端天冬酰胺或谷氨酰胺的肽的固相合成。一种基于Nα-芴甲氧羰基（Fmoc）保护和侧链锚定到三（烷氧基）苄酰胺（PAL）手柄的有效、温和方法。

Solid-phase synthesis of peptides with C-terminal asparagine or glutamine. An effective, mild procedure based on N alpha-fluorenylmethyloxycarbonyl (Fmoc) protection and side-chain anchoring to a tris(alkoxy)benzylamide (PAL) handle.

作者信息

Albericio F, van Abel R, Barany G

机构信息

Department of Chemistry, University of Minnesota, Minneapolis.

出版信息

Int J Pept Protein Res. 1990 Mar;35(3):284-6.

PMID:2354880

Abstract

Attempts to anchor Fmoc-asparagine or glutamine as p-alkoxybenzyl esters for solid-phase peptide synthesis are fraught with difficulties. A convenient and effective method to prepare peptides with C-terminal asparagine or glutamine involves quantitative attachment of N alpha-Fmoc-C alpha-tert.-butyl aspartate or glutamate via the free omega-carboxyl groups to a tris(alkoxy)benzylamino (PAL) support. Chain elongation proceeds normally by standard Fmoc chemistry, and treatment with acid, e.g., CF3COOH--CH2Cl2, 90 min at 25 degrees, releases the desired peptides in greater than 95% yields without side reactions at the C-terminus. Feasibility of the approach has been demonstrated by the syntheses of the C-terminal octapeptide from human proinsulin, H-Leu-Ala-Leu-Glu-Gly-Ser-Leu-Gln-OH, and the serum thymic factor pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH.

摘要

尝试将Fmoc - 天冬酰胺或谷氨酰胺作为对烷氧基苄酯用于固相肽合成充满困难。一种制备具有C端天冬酰胺或谷氨酰胺的肽的简便有效方法，是通过游离的ω - 羧基将Nα - Fmoc - Cα - 叔丁基天冬氨酸或谷氨酸定量连接到三（烷氧基）苄基氨基（PAL）载体上。通过标准的Fmoc化学方法正常进行链延伸，用酸处理，例如在25℃下用CF3COOH - CH2Cl2处理90分钟，以大于95％的产率释放所需的肽，且在C端无副反应。该方法的可行性已通过合成人胰岛素原的C端八肽H - Leu - Ala - Leu - Glu - Gly - Ser - Leu - Gln - OH以及血清胸腺因子pGlu - Ala - Lys - Ser - Gln - Gly - Gly - Ser - Asn - OH得到证明。