Synthesis and screening of small-molecule α-helix mimetic libraries targeting protein–protein interactions. (February 2015)

• Record Type: Journal Article
• Authors: Moon, Heejo; Lim, Hyun-Suk
• Is Part Of: Current opinion in chemical biology. Volume 24(2015)
• Page Start: 38
• Page End: 47
• Publication Date: 2015-02
• Subjects: Bioorganic chemistry -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Clinical biochemistry -- Periodicals; Biochemistry -- Periodicals; Chimie bio-organique -- Périodiques; Biologie -- Périodiques; 572.05
• DOI: 10.1016/j.cbpa.2014.10.023
• Languages: English
• ISSNs: 1367-5931

Abstract

Highlights: We highlight recent development of small-molecule α-helix mimetics. We review solid-phase synthesis of small-molecule α-helix mimetics. We highlight HTS methods for the identification of small-molecule α-helix mimetics. Abstract : α-Helices are the most common protein secondary structure and play a key role in mediating many protein–protein interactions (PPIs) by serving as recognition motifs. Given that aberrant α-helix-mediated PPIs are linked to various disease states, targeting such interactions with small-molecules represents an attractive strategy to develop therapeutic candidates for the related diseases. Over the last decade, significant efforts have been directed toward developing α-helix mimetic small-molecules that can modulate α-helix-mediated PPIs. In this review, we will highlight recent advances in the development of non-peptidic, small-molecule α-helix mimetics with a focus on library synthesis and screening methods to efficiently discover small-molecule α-helix mimetics.