254990-96-0Relevant academic research and scientific papers
Expanding the utility of proteases in synthesis: Broadening the substrate acceptance in non-coded amide bond formation using chemically modified mutants of subtilisin
Khumtaveeporn, Kanjai,Ullmann, Astrid,Matsumoto, Kazutsugu,Davis, Benjamin G.,Jones
, p. 249 - 261 (2007/10/03)
The strategy of combined site directed mutagenesis and chemical modification creates chemically modified mutants (CMMs) with greatly broadened substrate specificities. We have previously reported that the CMMs of subtilisin Bacillus lentus (SBL) are efficient catalysts for the coupling of both L- and D-amino acids. We now report that these powerful catalysts also allow amide bond formation between a variety of non-coded carboxylic acids, including β-alanine and β-amino homologues of phenylalanine, with both L- and D-amino acid nucleophiles. As a guide to enzyme efficiency, a hydrolysis assay indicating pH change has been employed. CMMs selected by this screen furnished higher yields of coupling products compared to the wild-type enzyme (WT). Furthermore, both WT and CMM enzymes allow highly stereoselective aminolysis of a meso diester with an amino acid amine. These results highlight the utility of CMMs in the efficient formation of non-coded amides as potential peptide isosteres.
Synthesis of asymmetrized 2-benzyl-1,3-diaminopropane by a chemoenzymatic route: A tool for combinatorially developing peptidomimetics
Banfi, Luca,Guanti, Giuseppe,Riva, Renata
, p. 3571 - 3592 (2007/10/03)
Both enantiomers of monoacetamide 5, together with 'dipeptides' 30a,b and monocarbamates 24, (R)-43 and (S)-43, all derived from 2-benzyl-1,3- diaminopropane 4, were synthesized by a chemoenzymatic route starting from the known monoacetate 12. The behaviour of 4 and of the bis(acylated) derivatives 8-11 with respect to hydrolytic enzymes is also presented, together with an extensive study on the configurational stability of monoacylated derivatives of 4.
