Bisubstrate ether-linked uridine-peptide conjugates as O-GlcNAc transferase inhibitors.

We report linear bisubstrate ether-linked uridine-peptide conjugates as OGT inhibitors having micromolar affinity. In vitro evaluation of the compounds revealed the importance of donor substrate, linker and acceptor substrate in the rational design of bisubstrate analogue inhibitors. Molecular dynamics simulations shed light on the binding of this novel class of inhibitors and rationalized the effect of amino acid truncation of acceptor peptide on OGT inhibition. PMID: 32991074 [PubMed - as supplied by publisher]

https://www.ncbi.nlm.nih.gov/pubmed/32991074?dopt=Abstract

Source: ChemMedChem - September 28, 2020 Category: Chemistry Authors: Rudrawar S, Makwana V, Ryan P, Malde AK, Anoopkumar-Dukie S Tags: ChemMedChem Source Type: research