Ribosomal
Synthesis of an Amphotericin‑B Inspired
Macrocycle
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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