An Improved Turn Structure for Inducing β-Hairpin Formation in Peptides

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2021 Jul 14

PMID 34258835

Citations 3

Authors

Xingyue Li

Andrew L Sabol

Michal Wierzbicki

Patrick J Salveson

James S Nowick

Affiliations

Soon will be listed here.

Abstract

Although β-hairpins are widespread in proteins, there is no tool to coax any small peptide to adopt a β-hairpin conformation, regardless of sequence. Here, we report that δ-linked γ(R)-methyl-ornithine ( MeOrn) provides an improved β-turn template for inducing a β-hairpin conformation in peptides. We developed a synthesis of protected MeOrn as a building block suitable for use in Fmoc-based solid-phase peptide synthesis. The synthesis begins with l-leucine and affords gram quantities of the N -Boc-N -Fmoc-γ(R)-methyl-ornithine building block. X-ray crystallography confirms that the MeOrn turn unit adopts a folded structure in a macrocyclic β-hairpin peptide. CD and NMR spectroscopy allow comparison of the MeOrn turn template to the δ-linked ornithine ( Orn) turn template that we previously introduced and to the popular d-Pro-Gly turn template. These studies show that the folding of the MeOrn turn template is substantially better than that of Orn and is comparable to d-Pro-Gly.

Citing Articles

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