7lib
X-ray crystal structure of a cyclic peptide containing beta-2-microglobulin (63-69) and a gamma-methylornithine turn unitX-ray crystal structure of a cyclic peptide containing beta-2-microglobulin (63-69) and a gamma-methylornithine turn unit
Structural highlights
Publication Abstract from PubMedAlthough beta-hairpins are widespread in proteins, there is still no universal tool to coax any small peptide to adopt a beta-hairpin conformation, regardless of sequence. Here, we report that delta-linked gamma( R )-methyl-ornithine ( delta MeOrn) provides an improved beta-turn template for inducing a beta-hairpin conformation in peptides. We have developed a synthesis of protected delta 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 alpha -Boc- N delta -Fmoc-gamma( R )-methyl-ornithine building block. X-ray crystallography confirms that the delta MeOrn turn unit adopts a folded structure in a macrocyclic beta-hairpin peptide. CD and NMR spectroscopic experiments allow comparison of the delta MeOrn turn template to the delta-linked ornithine ( delta Orn) turn template that our laboratory has previously introduced and also to the popular d -Pro-Gly turn template. Collectively, these studies demonstrate that the folding of the delta MeOrn turn template is substantially better than that of delta Orn and is comparable to d -Pro-Gly. An Improved Turn Structure for Inducing beta-Hairpin Formation in Peptides.,Nowick JS, Li X, Sabol AL, Wierzbicki M, Salveson PJ Angew Chem Int Ed Engl. 2021 Jul 13. doi: 10.1002/anie.202105559. PMID:34258835[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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