Queuine analogues incorporating the 7-aminomethyl-7-deazaguanine core: structure-activity relationships in the treatment of experimental autoimmune encephalomyelitis.

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.