Butelase‐Mediated Macrocyclization of d‐Amino‐Acid‐Containing Peptides. (14th September 2016)

• Record Type: Journal Article
• Authors: Nguyen, Giang K. T.; Hemu, Xinya; Quek, Jun‐Ping; Tam, James P.
• Is Part Of: Angewandte Chemie. Volume 128:Number 41(2016)
• Page Start: 12994
• Page End: 12998
• Publication Date: 2016-09-14
• Subjects: d-Aminosäuren -- Antibiotika -- Cyclisierungen -- Enzyme -- Peptide; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201607188
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Macrocyclic compounds have received increasing attention in recent years. With their large surface area, they hold promise for inhibiting protein–protein interactions, a chemical space that was thought to be undruggable. Although many chemical methods have been developed for peptide macrocyclization, enzymatic methods have emerged as a promising new economical approach. Thus far, most enzymes have been shown to act onl ‐peptides; their ability to cyclized ‐amino‐acid‐containing peptides has rarely been documented. Herein we show that macrocycles consisting ofd ‐amino acids, except for the Asn residue at the ligating site, were efficiently synthesized by butelase 1, an Asn/Asp‐specific ligase. Furthermore, by using a peptide‐library approach, we show that butelase 1 tolerates most of thed ‐amino acid residues at the P1′′ and P2′′ positions.