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Chemical Synthesis of Six‐Atom Thioether Bridged Diaminodiacid for Solid‐Phase Synthesis of Peptide Disulfide Bond Mimics
Author(s) -
Chen Junyou,
Sun Shuaishuai,
Zhao Rui,
Xi ChenPeng,
Qiu Wenjie,
Wang Ning,
Wang Ya,
Bierer Donald,
Shi Jing,
Li YiMing
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201904042
Subject(s) - thioether , disulfide bond , side chain , peptide , chemistry , peptide synthesis , solid phase synthesis , stereochemistry , thiol , combinatorial chemistry , group (periodic table) , organic chemistry , biochemistry , polymer
Solid phase peptide synthesis (SPPS) strategy based on diaminodiacids had become an effective method for the synthesis of disulfide‐containing polypeptides. At present, it remains necessary to develop a diaminodiacid with more abundant chain structures to study the structure‐activity relationship. In this work, we developed a new type of diaminodiacids containing a six‐atom thioether (C−C‐S−C‐C−C, C−C‐C−S‐C−C) bridge. The key segment protected homo‐homocystine can be efficiently obtained by converting a side chain carboxyl group into a thiol group, which contribute to the facile and efficient synthesis of new diaminodiacid. With this diaminodiacid in hand, we successfully obtained tachyplesin containing new disulfide bond mimic by solid phase peptide synthesis. The tachyplesin analog not only has similar activity as natural counterpart, but also exhibits increased stability under reducing conditions.