Catalysis of amide synthesis by RNA phosphodiester and hydroxyl groups.

ABSTRACT: The functional groups found among the RNA bases and in the phosphoribose backbone represent a limited repertoire from which to construct a ribozyme active site. This work investigates the possibility that simple RNA phosphodiester and hydroxyl functional groups could catalyze amide bond synthesis. Reaction of amine groups with activated esters would be catalyzed by a group that stabilizes the partial positive charge on the amine nucleophile in the transition state. 2'-Amine substitutions adjacent to 3'-phosphodiester or 3'-hydroxyl groups react efficiently with activated esters to form 2'-amide and peptide products. In contrast, analogs in which the 3'-phosphodiester is replaced by an uncharged phosphotriester or is constrained in a distal conformation react at least 100-fold more slowly.

SUBMITTER: Chamberlin SI 

PROVIDER: S-EPMC137480 | biostudies-literature | 2002 Nov

REPOSITORIES: biostudies-literature