Traceless Peptide Backbone Editing via Bio-inspired Cysteine to Thiazole Conversion
Year: 2025
Type: preprint
Abstract: Late-stage peptide modification is an important strategy for exploiting and expanding peptide bioactivity. While numerous methods exist for side-chain functionalization, chemical approaches for backbone editing remain limited. Inspired by the natural, enzyme-mediated conversion of cysteine to thiazole within peptides, we developed a traceless “label-and-edit” strategy for the backbone modification of cysteine-containing peptides. This method involves selective, biocompatible labeling of cysteine thiols with bromoacetophenone, followed by photoinduced thioaldehyde/enethiol formation and subsequent SH/amide cyclization to generate thiazole-containing peptides. A broad range of synthetic and natural peptides are compati-ble with this transformation, demonstrating its value as a versatile platform for late-stage peptide modification.
Source: ChemRxiv
Authors: Sen Zhang, Hongye Wang, Ashvin Nair, John Qiu, William Bancroft, Meg Shieh, Luofan Peng, Ming Xian
Institution: Brown University
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4417455255