Premium
Cover Picture: Ribosomal Synthesis of Backbone‐Macrocyclic Peptides Containing γ‐Amino Acids (ChemBioChem 8/2011)
Author(s) -
Ohshiro Yukinori,
Nakajima Eiji,
Goto Yuki,
Fuse Shinichiro,
Takahashi Takashi,
Doi Takayuki,
Suga Hiroaki
Publication year - 2011
Publication title -
chembiochem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201190031
Subject(s) - amino acid , peptide , chemistry , stereochemistry , transfer rna , peptide synthesis , peptide bond , genetic code , thioester , peptide sequence , biochemistry , enzyme , rna , gene
The cover picture shows ribosomal synthesis of backbone macrocyclic peptides containing γ‐amino acids. γ‐Amino acids are notoriously difficult to incorporate into a peptide chain by elongation, but this work gets around the problem by initiating the translation using γ‐aminoacyl‐phenylalanine (γaa‐F) dipeptides, and cyclizing the backbone. Because the N‐terminal γ‐amino group and the carbonyl of the C‐terminal residue were ligated via a peptide bond, the γ‐amino acid is embedded in the middle of sequence of peptide chain. To cyclize the backbone, genetic code reprogramming was used to install a sequence of cystidyl‐prolyl‐glycolate (C‐P‐ HO G), which self‐rearranges into a diketopiperadine (dkp) thioester and spontaneously macrocyclizes via the nucleophilic attack of the N‐terminal γ‐amino group to the dkp‐thioester. In the background is the tertiary structure of a tRNA–flexizyme (a critical enzyme used for the preparation of γaa‐F‐tRNA as well as HO G‐tRNA) complex. This illustration was created by Y. Goto with valuable suggestions from K. Futai. For more information see the paper by H. Suga et al. on p. 1183 ff.