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Continuous‐Flow Solid‐Phase Peptide Synthesis: A Revolutionary Reduction of the Amino Acid Excess
Author(s) -
Mándity István M.,
Olasz Balázs,
Ötvös Sándor B.,
Fülöp Ferenc
Publication year - 2014
Publication title -
chemsuschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.412
H-Index - 157
eISSN - 1864-564X
pISSN - 1864-5631
DOI - 10.1002/cssc.201402436
Subject(s) - amino acid , chemistry , peptide , alicyclic compound , solvent , peptide synthesis , combinatorial chemistry , continuous flow , organic chemistry , biochemistry , biochemical engineering , engineering
Abstract A highly efficient continuous‐flow technique for the synthesis of peptides was developed. The method allows the application of only 1.5 equivalents of amino acids during coupling, while yielding virtually quantitative conversions. A mesoscale reactor was constructed which permits the use of high temperature and pressure during the synthesis. A complete reaction parameter optimization was carried out. Under the optimum conditions, the couplings of all 20 proteinogenic amino acids were achieved with 1.5 amino acid equivalents with quantitative conversions. As a demonstration of the efficiency of the methodology, difficult sequences and β‐peptide foldamers with alicyclic side‐chains were synthetized in excellent yields and with lower costs thanks to the lower amounts of amino acid and solvent used. By this the synthesis is highly economic and sustainable. Importantly, exotic and expensive artificial amino acids were incorporated into peptidic sequences by the utilization of a reasonable number of amino acid equivalents. The synthesis can be performed in quantities of microgram to gram in an automated way.