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

Abstract

It was previously found that a cationic amphiphilic peptide, Ac-(Leu-Ala-Arg-Leu)3-NHCH3 (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 alpha-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), [Gln3]4(3), [Gln3,7]4(3) and [Gln3,7,11]4(3) were synthesized. Except for [Val2,6]4(3) and [Val2,6,10]4(3), which mainly formed a beta-structure, other peptides formed an alpha-helix and showed moderate membrane-perturbing activity toward neutral and acidic lipid vesicles. All the peptides other than [Val2,6,10]4(3) and [Gln3,7,10]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.

Interaction of pleurocidin and its analogs with phospholipid membrane and their antibacterial activity

“…This result seems to be reasonable based on its α‐helicity, and leakage and hemolytic activities. The fact that [A 13,17 ]Ple and [A 1,3,13,17 ]Ple had stronger antibacterial activity than [A 11,15,23 ]Ple is compatible with our previous view that amphiphilicity is more important than hydrophobicity for antibacterial activity (25), because the hydrophobicity value of [A 11,15,23 ]Ple is far higher than that of [A 13,17 ]Ple and [A 1,3,13,17 ]Ple (Table 2).…”

Cationic oligopeptides modified with lipophilic fragments: Use for DNA delivery to cells

“…The search for effective methods of systemic delivery of genes to eukaryotic cells is one of the most important areas of development of gene therapy [1][2][3][4]. 2 Three approaches are mainly used for the insertion of marker or "therapeutic" genes into cDNA: (1) application of recombinant viral vectors; (2) physical transfection methods (such as electroporation, DNA injections, "gene gun" method, and others); and (3) the application of nonviral systems for the DNA delivery to cells [5,6].…”

Transformação genética de laranja doce (Citrus sinensis L. Osbeck) com o gene D4E1 dirigido pelos promotores CaMV35S ou AtPP2

“…Existem vários tipos de estruturas e atividades contra bactérias, fungos, vírus e protozoários, sendo que todos agem na destruição da integridade de membranas celulares (NIIDOME et al, 1999). Em plantas, esses peptídeos podem ser produzidos constitutivamente ou somente quando a mesma sofre algum tipo de injúria ou infecção (GABAY, 1994 ), mantidas a -80 ºC.…”