Design of Model Amphipathic Peptides Having Potent Antimicrobial Activities Article

Blondelle, SE, Houghten, RA. (1992). Design of Model Amphipathic Peptides Having Potent Antimicrobial Activities . BIOCHEMISTRY, 31(50), 12688-12694. 10.1021/bi00165a020

cited authors

  • Blondelle, SE; Houghten, RA

abstract

  • Induced amphipathic α-helical conformations play an important role in the biological activity of peptides. By using reversed-phase high-performance liquid chromatography (RP-HPLC) as a means to study the secondary structure of peptides at aqueous/lipid interfaces, a sequence (Ac-LKLLKKLL-KKLKKLLKKL-NH2) was found to readily adopt an amphipathic α-helical conformation upon interacting with the lipid groups of the stationary phase during RP-HPLC. This peptide exhibited potent antimicrobial activities against both Gram-positive and Gram-negative bacteria. We have prepared a complete set of omission, as well as of leucine and lysine substitution, analogs of this sequence. These analogs were used to investigate the effects of such alterations on the parent sequence's antimicrobial and hemolytic activities relative to each analog's behavior during RP-HPLC. The potential for the formation of ion channels through cell membranes by this amphipathic model peptide was also evaluated through preparation of analogs which varied in length from 8 to 22 residues, while maintaining their amphipathicity. © 1992, American Chemical Society. All rights reserved.

publication date

  • February 1, 1992

published in

Digital Object Identifier (DOI)

start page

  • 12688

end page

  • 12694

volume

  • 31

issue

  • 50