Disulfide Bond Mimetics: Strategies and Challenges. Issue 60 (23rd August 2017)

• Record Type: Journal Article
• Authors: Gori, Alessandro; Gagni, Paola; Rinaldi, Silvia
• Is Part Of: Chemistry. Volume 23:Issue 60(2017)
• Page Start: 14987
• Page End: 14995
• Publication Date: 2017-08-23
• Subjects: cyclic peptides -- disulfide isosters -- drug discovery -- peptidomimetics -- protein folding; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201703199
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: The activity profile of many biologically relevant proteins and peptides often relies on a precise 3D structural organization. In this context, disulfide bonds are natural covalent constraints that play a key role in driving and stabilizing the folding pattern of these molecules. Despite its prominent significance as structural motif, the disulfide bond itself is inherently unstable under physiological conditions, posing a major limit to the use and development of disulfide‐rich peptides and proteins as molecular tools and drug lead compounds. To tackle this restriction, disulfide engineering with stable functional analogues has arisen a considerable interest. Here, the most popular approaches to disulfide replacement are reviewed and discussed with particular emphasis on advantages and limitations under both functional and synthetic perspectives. Abstract : Make it tough : The most common strategies to disulfide bond mimetics are dissected and emerging approaches presented. Functional and synthetic aspects towards disulfide engineering are critically discussed.