Ribosomal Translation and Display Selection of Cyclic Glycopeptides through Genetic Reprogramming

Journal of the American Chemical Society 2026

View at publisher
Authors: Jason Johansen-Leete, Yichen Zhong, Beiyuan Cui, Bernardo Cavallazzi Sebold, Lucas Kambanis, Caitlin E. Clarke-Shepperson, Christopher Lehmann, Ka Hin Toby Mak, Arthur H. Tang, James G. Burchfield, Walter Ferreira Becker, José Perdomo
+6 more D McDonald, Leo Corcilius, Toby Passioura, Freda Passam, Daniel Ford, Richard J. Payne
DOI: 10.1021/jacs.5c22682
Cited by: 2
References: 39

Abstract

A robust method for the ribosomal incorporation of glycosyl-amino acids through the flexizyme-mediated reprogramming of initiating AUG codons with glycosyl-dipeptides is described. This reprogramming strategy was applied to in vitro mRNA display for the de novo discovery of α- l -fucosylated cyclic peptide inhibitors of P-selectin with antiplatelet-monocyte aggregation activity, and β- d -N-acetylgalactosamine-containing cyclic glycopeptide agonists of the asialoglycoprotein receptor (ASGPR) with potent lysosome trafficking activity. This work provides a powerful platform for the de novo discovery of glycopeptide ligands and expands genetic reprogramming capabilities to large modifications previously intractable for ribosomal translation.

Fields of Study & Subjects

RNA and protein synthesis mechanisms Glycosylation and Glycoproteins Research Microbial Natural Products and Biosynthesis

Publication details

Journal / source
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Volume
148
Issue
10
Pages
10321–10328
Publication date
4 March 2026
Language
EN