Chemical Synthesis of Six‐Atom Thioether Bridged Diaminodiacid for Solid‐Phase Synthesis of Peptide Disulfide Bond Mimics. Issue 4 (24th January 2020)

• Record Type: Journal Article
• Authors: Chen, Junyou; Sun, Shuaishuai; Zhao, Rui; Xi, Chen‐Peng; Qiu, Wenjie; Wang, Ning; Wang, Ya; Bierer, Donald; Shi, Jing; Li, Yi‐Ming
• Is Part Of: ChemistrySelect. Volume 5:Issue 4(2020)
• Page Start: 1359
• Page End: 1363
• Publication Date: 2020-01-24
• Subjects: Disulfide bond mimetic -- Diaminodiacid -- Six-atom thioether bridge -- Tachyplesin mimic; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201904042
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: 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. Abstract : We successfully synthesized six‐atom diaminodiacid for the first time, and the key unit can be efficiently prepared by a new method for converting a side chain carboxyl group into a thiol group. The diaminodiacid applied to synthesis TPI peptide analog. The utility of this diaminodiacid is demonstrated in the synthesis of tachyplesin disulfide analogues, which not only had good activity but also increased stability under reducing conditions.