Derivatives of N-amidinoproline and their use in conventional and solid phase peptide synthesis

Abstract

N-Amidinoproline, a hybrid structure modeling key features of the Arg-Pro sequence, was synthesized. The activation of carboxyl group of free N-amidinoproline was found to result in the formation of a cyclic side product, whose structure was confirmed by ESI MS, 1H NMR, and 13C NMR spectra. The preparation of N-(mesitylenesulfonylamidino)-L-proline using the mesitylenesulfonyl derivative of 2-methylisourea was demonstrated to be accompanied by partial racemization. The target product was synthesized by modification of N-amidinoproline by mesitylenesulfonyl chloride. The possibility of using N-amidinoproline in the N-terminal modification of a peptide chain was shown by the example of synthesis of an analogue of the 95-98 fragment of fibrinogen alpha chain.

Incorporation of N‐amidino‐pyroglutamic acid into peptides using intramolecular cyclization of α‐guanidinoglutaric acid

“…Previously we described synthesis of N ‐amidino‐proline and its derivatives for the application in classical and solid‐phase peptide synthesis12. These data prompted us to investigate the practical utility of N ‐amidino‐proline oxidation leading to the formation of N ‐amidino‐pyroglutamic acid.…”

“…Among different cyclization reagents, described in the literature28–30, DIC/HOBt seems appropriate for this case. The guanidinylation was performed using Boc 2 CABt/DIEA in accordance with procedure for synthesis of peptides containing N ‐amidino‐proline12. However, we encountered multiple problems at the stage of peptide cleavage.…”

“…N ‐amidino‐L‐proline was synthesized as reported elsewhere12. Briefly, L‐ proline was guanidinylated with cyanamide in water–methanol solution and purified by precipitation in isopropyl alcohol and recrystallization from water.…”