Interactions between the plasma membrane and the antimicrobial peptide HP (2-20) and its analogues derived from Helicobacter pylori

• DOI: 10.1042/bj20051574
• Publication Date: 2006-03-02T09:17:57Z
• Authors: Kwang H. Lee; Dong G. Lee; Yoonkyung Park; Dong-Il Kang; Song Y. Shin; Kyung-Soo Hahm; Yangmee Kim
• Keywords: Models, Molecular; 0301 basic medicine; Erythrocytes; Dose-Response Relationship, Drug; Helicobacter pylori; Sequence Homology, Amino Acid; Protein Conformation; Cell Membrane; Fungi; Tryptophan; Peptide Fragments; 03 medical and health sciences; Anti-Infective Agents; Bacterial Proteins; Amino Acid Sequence; Cell Shape; Hydrophobic and Hydrophilic Interactions; Protein Binding

HP (2-20), a 19-residue peptide derived from the N-terminus of Helicobacter pylori ribosomal protein L1, has antimicrobial activity but is not cytotoxic to human erythrocytes. We synthesized several analogues investigate effects substitutions on structure and activity. Replacement Gln16 Asp18 with tryptophan [anal-3 (analogue-3)] caused dramatic increase in lytic activities against bacteria fungi. By contrast, decrease amphiphilicity by replacement Phe5 or Leu11 serine was accompanied reduction Analysis tertiary structures peptides SDS micelles NMR spectroscopy revealed that they have well-defined α-helical structure. Among analogues, anal-3 longest α-helix, Val4 Trp18. The enhanced hydrophobicity increased α-helicity results without an haemolytic Fluorescence experiments proved bacterial-cell selectivity due its high binding affinity for negatively charged phospholipids bacterial cells. Results showing effect spin-labels spectra indicated side chains hydrophobic phase amphiphilic α-helix are buried surface micelle indole ring anchored membrane surface. Because shows towards fungal cells, it may provide avenue development new antibiotics.