286458-65-9Relevant articles and documents
Unexpected preference of the E. coli translation system for the ester bond during incorporation of backbone-elongated substrates
Sando, Shinsuke,Abe, Kenji,Sato, Nobuhiko,Shibata, Toshihiro,Mizusawa, Keigo,Aoyama, Yasuhiro
, p. 6180 - 6186 (2007)
There have been recent advances in the ribosomal synthesis of various molecules composed of nonnatural ribosomal substrates. However, the ribosome has strict limitations on substrates with elongated backbones. Here, we show an unexpected loophole in the E. coli translation system, based on a remarkable disparity in its selectivity for β-amino/hydroxy acids. We challenged β-hydroxypropionic acid (β-HPA), which is less nucleophilic than β-amino acids but free from protonation, to produce a new repertoire of ribosome-compatible but main-chain-elongated substrates. PAGE analysis and mass-coupled S-tag assays of amber suppression experiments using yeast suppressor tRNAPheCUA confirmed the actual incorporation of β-HPA into proteins/oligopeptides. We investigated the side-chain effects of β-HPA and found that the side chain at position α and R stereochemistry of the β-substrate is preferred and even notably enhances the efficiency of incorporation as compared to the parent substrate. These results indicate that the E. coli translation machinery can utilize main-chain-elongated substrates if the pKa of the substrate is appropriately chosen.
Efficient synthesis of the C1-C11 fragment of the tedanolides. The nonaldol aldol process in synthesis
Jung, Michael E.,Marquez, Rodolfo
, p. 1669 - 1672 (2007/10/03)
(matrix presented) The nonaldol aldol process developed in our laboratories has been applied to the synthesis of a C1-C11 fragment 22 of the novel macrocyclic cytotoxic agents tedanolide and 13-deoxytedanolide 1 and 2. The commercially available hydroxy ester 7 was converted in 24 steps into compound 22 using two nonaldol aldol reactions.
