Abstract
Intermolecular hydrophobic interactions between the indole or phenyl moieties of the peptides containing L‐tryptophan (L‐Trp) or L‐phenylalanine (L‐Phe) residues and the apolar isopropyl groups of the peptides containing L‐leucine (L‐Leu) or L‐valine (L‐Val) in aqueous solutions have been detected by ^1^H NMR by monitoring the observed changes in the proton magnetic resonance parameters of the methyl resonances of the peptides containing L‐Leu or L‐Val residues. The ^1^H NMR data indicate that intermolecular hydrophobic interactions are responsible for the observed changes in the proton magnetic resonance parameters of the methyl resonances. For example, when a solution of glycylglycylleucine (Gly‐Gly‐L‐Leu) in deuterium oxide was mixed with glycylglycyltryptophan (Gly‐Gly‐L‐Trp), the methyl protons of Gly‐Gly‐L‐Leu exhibited large diamagnetic ring current shifts. However, when glycylglycylglycine (Gly‐Gly‐Gly) was substituted for Gly‐Gly‐L‐Trp in the NMR experiment, the methyl resonances did not show any upfield or downfield shift, thereby demonstrating that the observed upfield shifts are not due to bulk susceptibility differences between solutions. The C‐terminus peptides containing L‐Leu or L‐Val residues bind to the aromatic L‐Trp or L‐Phe peptides better than the N‐terminus L‐Leu or L‐Val peptides. The C‐terminus Gly‐Gly‐L‐Leu binds better than the C‐terminus glycylglycylvaline (Gly‐Gly‐L‐Val). The strength and specificity of hydrophobic interactions in several small peptides are discussed.