title: Ribosomal synthesis of an amphotericin-B inspired macrocycle.
abstract: Here we report in vitro ribosomal synthesis of a natural product-like macrocyclic peptide, inspired by the structure of amphotericin B (AmB), an amphiphilic and membrane-interacting antifungal natural product. This AmB-inspired macrocyclic peptide (AmP), one side of which is composed of hydrophobic terpene, and the other side comprises a peptidic chain, was synthesized utilizing flexizyme-assisted in vitro translation via an unusual but successful initiation with a D-cysteine derivative. The established method for the synthesis of AmPs is applicable to the generation of a diverse AmP library coupled with an in vitro display format, with the potential to lead to the discovery of artificial bioactive amphiphilic macrocycles.
authors.affiliation: Department of Chemistry, Graduate School of Science, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Torikai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suga
mesh_terms: D000666:Amphotericin B / Q000096:biosynthesis* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D047028:Macrocyclic Compounds / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D047028:Macrocyclic Compounds; D000666:Amphotericin B