Queuine Analogues Incorporating the 7-Aminomethyl-7-deazaguanine Core: Structure-Activity Relationships in the Treatment of Experimental Autoimmune Encephalomyelitis

Michelle Cotter; Sreeja Varghese; Franciane Chevot; Claire Fergus; Vincent P Kelly; Stephen J Connon; J Mike Southern

doi:10.1002/cmdc.202300207

Queuine Analogues Incorporating the 7-Aminomethyl-7-deazaguanine Core: Structure-Activity Relationships in the Treatment of Experimental Autoimmune Encephalomyelitis

ChemMedChem. 2023 Sep 1;18(17):e202300207. doi: 10.1002/cmdc.202300207. Epub 2023 Jul 21.

Authors

Michelle Cotter¹, Sreeja Varghese², Franciane Chevot¹, Claire Fergus², Vincent P Kelly², Stephen J Connon¹, J Mike Southern¹

Affiliations

¹ School of Chemistry, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Trinity College, Dublin, Ireland.
² School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Trinity College, Dublin, Ireland.

PMID: 37350546
DOI: 10.1002/cmdc.202300207

Abstract

A library of queuine analogues targeting the modification of tRNA isoacceptors for Asp, Asn, His and Tyr catalysed by queuine tRNA ribosyltransferase (QTRT, also known as TGT) was evaluated in the treatment of a chronic multiple sclerosis model: murine experimental autoimmune encephalomyelitis. Several active 7-deazaguanines emerged, together with a structure-activity relationship involving the necessity for a flexible alkyl chain of fixed length.

Keywords: RNA modifications; experimental autoimmune encephalomyelitis; multiple sclerosis; queuine; transfer RNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Encephalomyelitis, Autoimmune, Experimental* / drug therapy
Mice
Pentosyltransferases / metabolism
RNA, Transfer
Structure-Activity Relationship

Substances

7-deazaguanine
queuine
RNA, Transfer
Pentosyltransferases