Effect of L-leucine graft content on aqueous solution behavior and membrane-lytic activity of a pH-responsive pseudopeptide. Academic Article uri icon

Overview

abstract

  • A series of pH-responsive polymers have been synthesized by grafting L-leucine onto the pendant carboxylic acid groups of the linear pseudopeptide, poly(L-lysine iso-phthalamide). The effect of the degree of grafting on aqueous solution properties, cell membrane-disruptive activity, and in vitro cytotoxicity was examined by UV-visible and fluorescence spectroscopy, hemolysis, alamar blue staining, and propidium iodide fluorescence assays. Modification of poly(L-lysine iso-phthalamide) with < or =23.6 mol % L-leucine caused a marginal effect on the pH-mediated hydrophobic association and hemolytic activity. Increasing the degree of grafting from 31.9 to 61.2 mol % resulted in polymers with progressively enhanced hydrophobic association and cell membrane disruption, thus confirming that the pH responsiveness and the extent of hydrophobic association and membrane disruption of the polymers can be modulated by varying the degree of grafting with hydrophobic amino acids. The pH responses were demonstrated to be concentration-dependent. At certain degrees of leucine grafting, the polymers were nonmembrane-lytic at physiological pH but mediated considerable membrane lysis at endosomal pH values (5.0-6.8), a feature critical for potential drug delivery applications.

publication date

  • September 14, 2009

Research

keywords

  • Cell Membrane Permeability
  • Drug Delivery Systems
  • Leucine
  • Phthalic Acids
  • Polylysine
  • Polymers

Identity

Scopus Document Identifier

  • 70349173316

Digital Object Identifier (DOI)

  • 10.1021/bm900534j

PubMed ID

  • 19642668

Additional Document Info

volume

  • 10

issue

  • 9