Relationship between the tertiary structures of mastoparan B and its analogs and their lytic activities studied by NMR spectroscopy

Mastoparan B (MP-B), an antimicrobial cationic tetradecapeptide amide isola ted from the venom of the hornet Vespa basalis, is an amphiphilic ct-helica l peptide. MP-B possesses a variety of biological activities, such as mast cells degradation histamine release, erythrocyte lysis and inhibition of th e growth of Cram-positive and Gram-negative bacteria. In order to study the relationship between the structure and the biological activity of MP-B, we used four analogs by replacing amino acids with alanine. Tertiary structur es of MP-B and its analogs in 2,2,2-trifluoroethanol (TFE)-containing aqueo us solution have been determined by NMR spectroscopy and molecular modeling . The results indicate that [Ala(4)]MP-B and [Ala(12)]MP-B with higher hydr ophobicity adopt a higher content of amphiphilic helical structures, and ha ve better antimicrobial and hemolytic activities than MP-B. However, [Ala(3 )]MP-B and [Ala(9)]MP-B with lower hydrophobicity have disordered structure s. [Ala3]MP-B and [Ala9]MP-B have low antimicrobial activity and much less hemolytic activity relative to NIP-B. It is likely that tryptophan residue in MP-B and appropriate hydrophobicity of MP-B to induce alpha-helical stru cture is essential for the antibacterial and hemolytic activity of MP-B. Th is study can aid understanding of the structure-activity relationship of MP -B and to design peptides to possess lytic activity.