Butelase‐Mediated Macrocyclization of d‐Amino‐Acid‐Containing Peptides |
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| Authors: | Dr Giang K T Nguyen Dr Xinya Hemu Jun‐Ping Quek Prof Dr James P Tam |
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| Affiliation: | School of Biological Sciences, Nanyang Technological University, Singapore, Singapore |
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| 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 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. |
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| Keywords: | d-amino acids antibiotics cyclization enzymes peptides |
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