Understanding the complex relationship between amino acid sequence and protein behaviors, such as folding and self-association, is a major goal of protein research. In the present work, we examined the effects of deleting a C-terminal residue on the intrinsic properties of an amphapathic α-helix of mastoparan-B (MP-B), an antimicrobial peptide with the sequence LKLKSIVSWAKKVL-NH2. We used circular dichroism and nuclear magnetic resonance to demonstrate that the peptide MP-B[1-13] displayed significant unwinding at the N-terminal helix compared with the parent peptide of MP-B, as the temperature increased when the residue at position 14 was deleted. Pulsed-field gradient nuclear magnetic resonance data revealed that MP-B forms a larger diffusion unit than MP-B[1-13] at all experimental temperatures and continuously dissociates as the temperature increases. In contrast, the size of the diffusion unit of MP-B[1-13] is almost independent of temperature. These findings suggest that deleting the flexible, hydrophobic amino acid from the C-terminus of MP-B is sufficient to change the intrinsic helical thermal stability and self-association. This effect is most likely because of the modulation of enthalpic interactions and conformational freedom that are specified by this residue. Our results implicate terminal residues in the biological function of an antimicrobial peptide. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
The roles of the C-terminal residue in peptide behaviors were examined. The association size of the peptides and their structures at various temperatures in 2,2,2-trifluoroethanol aqueous solution were monitored and characterized with nuclear magnetic resonance methods. The structural and functional relevance of the terminus demonstrated in this work is potentially relevant for the design of potent substances that may serve as drug candidates.