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Synthesis of Constrained Tetracyclic Peptides by Consecutive CEPS, CLIPS, and Oxime Ligation
journal contribution
posted on 2019-03-26, 12:08 authored by Dieuwertje
E. Streefkerk, Marcel Schmidt, Johannes H. Ippel, Tilman M. Hackeng, Timo Nuijens, Peter Timmerman, Jan H. van MaarseveenIn Nature, multicyclic
peptides constitute a versatile molecule
class with various biological functions. For their pharmaceutical
exploitation, chemical methodologies that enable selective consecutive
macrocyclizations are required. We disclose a combination of enzymatic
macrocyclization, CLIPS alkylation, and oxime ligation to prepare
tetracyclic peptides. Five new small molecular scaffolds and differently
sized model peptides featuring noncanonical amino acids were synthesized.
Enzymatic macrocyclization, followed by one-pot scaffold-assisted
cyclizations, yielded 21 tetracyclic peptides in a facile and robust
manner.