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Butelase‐Mediated Macrocyclization of d ‐Amino‐Acid‐Containing Peptides
Author(s) -
Nguyen Giang K. T.,
Hemu Xinya,
Quek JunPing,
Tam James P.
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201607188
Subject(s) - peptide , amino acid , amino acid residue , residue (chemistry) , chemistry , enzyme , combinatorial chemistry , chemical space , biochemistry , stereochemistry , peptide sequence , dna ligase , drug discovery , gene
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 on l ‐peptides; their ability to cyclize d ‐amino‐acid‐containing peptides has rarely been documented. Herein we show that macrocycles consisting of d ‐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 the d ‐amino acid residues at the P1′′ and P2′′ positions.