Role of two consecutive α,β-dehydrophenylalanines in peptide structure: Crystal and molecular structure of Boc-Leu-ΔPhe-ΔPhe-Ala-Phe-NHMe

Abstract

An Nα‐protected model pentapeptide containing two consecutive ΔPhe residues, Boc‐Leu‐ΔPhe‐ΔPhe‐Ala‐Phe‐NHMe, has been synthesized by solution methods and fully characterized. 1H‐nmr studies provided evidence for the occurrence of a significant population of a conformer having three consecutive, intramolecularly H‐bonded β‐bends in solution. The solid state structure has been determined by x‐ray diffraction methods. The crystals grown from aqueous methanol are orthorhombic, space group P212121, a = 11.503(2), b = 16.554(2), c = 22.107(3) Å, V = 4209(1) Å,3 and Z = 4. The x‐ray data were collected on a CAD4 diffractometer using CuKa radiation (λ = 1.5418 Å). The structure was determined using direct methods and refined by full‐matrix least‐squares procedure. The R factor is 5.3%. The molecule is characterized by a right handed 310‐helical conformation (〈ϕ〉 = −68.2°, 〈ψ〉 = −26.3°), which is made up of two consecutive type III β‐bends and one type I β‐bend. In the solid state the helical molecules are aligned head‐to‐tail, thus forming long rod like structures. A comparison with other peptide structures containing consecutive ΔPhe residues is also provided. The present study confirms that the ‐ΔPhe‐ΔPhe‐sequence can be accommodated in helical structures. © 1997 John Wiley & Sons, Inc. Biopoly 42: 373–382, 1997

Peptide design using α,β‐dehydro amino acids: From β‐turns to helical hairpins

“…In BocAlaΔPheΔPheNHMe, Tuzi et al31 found two independent molecules in the crystallographic unit; a right‐handed and a left‐handed 3 10 ‐helix. In most peptides containing two consecutive ΔPhe residues such as BocValΔPheΔPheValOMe or BocLeuΔPheΔPheAlaPheNHMe, a well‐aligned right‐handed 3 10 ‐helical conformation is stabilized 79–82. It can be speculated that consecutive ΔPhe‐containing peptides possessing bulky L residues favor the formation of a right‐handed 3 10 ‐helix.…”

Crystal structure of Boc‐LAla‐ΔPhe‐ΔPhe‐ΔPhe‐ΔPhe‐NHMe: a left‐handed helical peptide

“…It may the 01-CS bond [e2, = -58.6", OZ2 = 65.0"~ e2, = 177.2~1. Circular dichroism studies were carried out to probe the (17,27,28).…”

Handedness preference and switching of peptide helices. Part II: Helices based on noncodedα‐amino acids

“…Privileged solution conformations of Δ Z Phe‐based peptides were satisfactorily determined by NMR analysis . Short peptides containing Δ Z Phe residues were generally shown to fold into conformations that may be perturbed by the H‐bonding capabilities of the solvent.…”

“…As in the case of the aforementioned Aib peptides discussed, many ΔPhe‐containing linear peptides are highly crystalline materials. This property allows X‐ray diffraction analyses to be performed . Almost all of them are characterized by the Δ Z Phe configurational isomer.…”