Chemoenzymatic synthesis of polypeptides in neat 1,1,1,2-tetrafluoroethane solvent

Chemoenzymatic polypeptide synthesis offers several advantages over chemical or other biological routes, however, the use of aqueous-based media suffers from reverse hydrolysis reactions that challenge peptide chain propagation. Herein, the protease from subtilisin Carlsberg biocatalyzed the synthes...

Full description

Saved in:
Bibliographic Details
Published in:RSC advances 2018-10, Vol.8 (63), p.35936-35945
Main Authors: Aguirre-Díaz, Isabel S, Montiel, Carmina, Bustos-Jaimes, Ismael, Medina-Gonzalez, Yaocihuatl, Tecante, Alberto, Gimeno, Miquel
Format: Article
Language:English
Subjects:
Chemical engineering
Chemical Sciences
Chemical synthesis
Chemistry
Dichroism
Esters
Ethyl esters
Hydrolysis
Molecular dynamics
Organic chemistry
Polypeptides
Propagation
Protease
Solvents
Structural analysis
Substrates
Tetrafluoroethane
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Chemoenzymatic polypeptide synthesis offers several advantages over chemical or other biological routes, however, the use of aqueous-based media suffers from reverse hydrolysis reactions that challenge peptide chain propagation. Herein, the protease from subtilisin Carlsberg biocatalyzed the synthesis of poly-l-PheOEt, poly-l-LeuOEt, and the copolymers poly-l-PheOEt- -l-LeuOEt from their amino acid ethyl ester substrates in a neat liquid 1,1,1,2-tetrafluoroethane solvent. The products, achieved in acceptable yields ( 50%), were fully characterized showing relatively high molar mass ( 20 000 Da for poly-l-PheOEt). This non-toxic low-boiling hydrofluorocarbon enhances enzymatic peptide propagation by limiting hydrolysis owing to its hydrophobic and relatively polar characteristics that sustain the protease activity and solubilize substrates and products. Computational molecular dynamic calculations were used to assess the l-PheOEt/l-LeuOEt-solvent and polypeptide-solvent interactions in this system. Additionally, the homopolypeptides displayed higher crystallinity than the copolypeptides with random incorporation of amino acid ethyl esters, notwithstanding the significantly highest specificity for Phe in this system. Interestingly, secondary structure characterization of the products by FTIR and circular dichroism suggests a non-common peptide folding.
ISSN:2046-2069
2046-2069
DOI:10.1039/c8ra06657d