Effect of amino acid substitution in amphiphilic α-helical peptides on peptide–phospholipid membrane interaction

✍ Scribed by Takuro Niidome; Shingo Anzai; Junko Sonoda; Yoko Tokunaga; Masaaki Nakahara; Tomomitsu Hatakeyama; Haruhiko Aoyagi

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 137 KB
• Volume: 5
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/(sici)1099-1387(199907)5:7<298::aid-psc197>3.0.co;2-5

✦ Synopsis

It was previously found that a cationic amphiphilic peptide, Ac-(Leu-Ala-Arg-Leu) 3 -NHCH 3 (4 3 ), caused the destabilization of a phospholipid membrane and showed strong antibacterial activity [Lee et al. Biochim. Biophys. Acta 1986; 862: 211 -219]. In order to investigate the effect of changing h-helix propensity, hydrophobicity and basicity in 4 3 on the peptide conformation and activity, the 4 3 analogs, [Gly (or Val) 6 ]4 3 , [Gly (or Val) 2,6 ]4 3 , [Gly (or Val) 2,6,10 ]4 3 , [Gln 3 ]4 3 , [Gln 3,7 ]4 3 and [Gln 3,7,11 ]4 3 were synthesized. Except for [Val 2,6 ]4 3 and [Val 2,6,10 ]4 3 , which mainly formed a i-structure, other peptides formed an h-helix and showed moderate membrane-perturbing activity toward neutral and acidic lipid vesicles. All the peptides other than [Val 2,6,10 ]4 3 and [Gln 3,7,10 ]4 3 had the antibacterial activity comparable with that of 4 3 . The relationship between the membrane-perturbing activity and the antibacterial activity was not always parallel. Conclusively, the Ala Val substitution in 4 3 causes the change of peptide conformation and the presence of a cationic amino acid residue is necessary for the antibacterial activity.