Ribosomal synthesis of N-methyl peptides.

ABSTRACT: N-methyl amino acids (N-Me AAs) are a common component of nonribosomal peptides (NRPs), a class of natural products from which many clinically important therapeutics are obtained. N-Me AAs confer peptides with increased conformational rigidity, membrane permeability, and protease resistance. Hence, these analogues are highly desirable building blocks in the ribosomal synthesis of unnatural peptide libraries, from which functional, NRP-like molecules may be identified. By supplementing a reconstituted Escherichia coli translation system with specifically aminoacylated total tRNA that has been chemically methylated, we have identified three N-Me AAs (N-Me Leu, N-Me Thr, and N-Me Val) that are efficiently incorporated into peptides by the ribosome. Moreover, we have demonstrated the synthesis

SUBMITTER: Subtelny AO 

PROVIDER: S-EPMC2728122 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature