Unwanted hydrolysis or α/β-peptide bond formation: how long should the rate-limiting coupling step take?

ABSTRACT: Nowadays, in Solid Phase Peptide Synthesis (SPPS), being either manual, automated, continuous flow or microwave-assisted, the reaction with various coupling reagents takes place via in situ active ester formation. In this study, the formation and stability of these key active esters were investigated with time-resolved ¹H NMR by using the common PyBOP/DIEA and HOBt/DIC coupling reagents for both α- and β-amino acids. Parallel to the amide bond formation, the hydrolysis of the α/β-active esters, a side reaction that is a considerable efficacy limiting factor, was studied. Based on the chemical nature/constitution of the active esters, three amino acid categories were determined: (i) the rapidly hydrolyzing ones (t < 6 h) with smaller (Ala) or even longer side chains

SUBMITTER: Goldschmidt Goz V 

PROVIDER: S-EPMC9072530 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature