Selective Aromatic Interactions in β-Hairpin Peptides

Abstract

To probe the selectivity possible in hydrophobic clusters, we have compared the cross-strand interactions of phenylalanine (Phe) and cyclohexylalanine (Cha) in a beta-hairpin peptide. We have found a preference for self-association among the aromatic residues, which provides 0.55 kcal/mol in stability relative to Cha-Cha cross-strand pair. NMR analysis of the Phe-Phe cross-strand pair indicates that it interacts in an edge-face interaction, despite the fact that it is highly solvent-exposed. The interaction geometry as well as the enthalpic and entropic values for the peptide containing the Phe-Phe cross-strand pair suggest that the preference for self-association arises from inherent differences in the nature of aromatic and aliphatic interactions in water.

β‐Hairpin Peptides: Heme Binding, Catalysis, and Structure in Detergent Micelles

“…The two Phe residues, at positions 2 and 7, in IV8 peptide may stabilize the b-hairpin structure through aromatic packing. [37][38][39][40] To correlate aromatic interactions of b-hairpin stability with activity, the analogue peptide IV8FA has been synthesized. Finally, the N-termini of the peptides are myristoylated (Myr) to achieve a stable insertion into lipid membranes.…”

Bindungsmechanismen in supramolekularen Komplexen

“…In Haarnadel-Modellen wurde für die Phe-Phe-Wechselwirkung innerhalb des Peptidstrangs ein Beitrag von etwa 2 kJ mol À1 abgeleitet. [506] Allerdings ergaben Analysen mit Oligomodellpeptiden, die Phenylalanin und Cyclohexylalanin in der Seitenkette tragen, keine Bevorzugung von Kombinationen mit nachbarständigen Phe-Phe-Einheiten. [507] Die Wechselwirkung zwischen Aminosäure-Seitenketten RG und aromatischen Einheiten RH einer synthetischen Wirtverbindung (Schema 15) ist eine effektive Strategie zur auch sequenzselektiven Erkennung von Peptiden.…”

Cross-Strand Coupling and Site-Specific Unfolding Thermodynamics of a Trpzip β-Hairpin Peptide Using 13C Isotopic Labeling and IR Spectroscopy

“…The resulting thermal denaturation curves are often characterized by very broad transitions. [43][44][45][46][47] Increase in the number of interstrand hydrophobic interactions has been shown to stabilize -hairpin structures and result in somewhat more sigmoidal denaturation profiles in trpzips; 1,30,48 however, there can be a tendency for such peptide sequences to aggregate. 24 Due to their small size, trpzips have also been a subject of many theoretical studies.…”