The effect of the placement and total charge of the basic amino acid clusters on antibacterial organism selectivity and potency

Resistin-like molecule β is a bactericidal protein that promotes spatial segregation of the microbiota and the colonic epithelium

“…2 A and B), indicating a preference for acidic phospholipids. Liposomes composed of PS alone also yielded a reduced rate of dye efflux, suggesting that charge density is an important factor for RELMβ membrane-disrupting activity, a characteristic shared with other cationic antimicrobial proteins (23,24). Thus, RELMβ preferentially permeabilizes negatively charged lipid membranes, consistent with the salt sensitivity of RELMβ bactericidal activity ( Fig.…”

Effect of Liposome Surface Charge and Peptide Side Chain Charge Density on Antimicrobial Peptide-Membrane Binding as Determined by Circular Dichroism

“…This is because changing the conformation of an AMP changes its amphipathic nature which in turn changes its physicochemical surface properties [27,43]. The changes in the conformation/physicochemical properties of the AMP will lead to different mechanisms of interaction with zwitter ionic and anionic liposomes and thus to organism selectivity [32,[44][45][46]. This observation was supported by ITC and calcein leakage data that indicated that these AMPs interact via very different mechanisms with anionic and zwitterionic LUVs [32,[44][45][46].…”

“…The changes in the conformation/physicochemical properties of the AMP will lead to different mechanisms of interaction with zwitter ionic and anionic liposomes and thus to organism selectivity [32,[44][45][46]. This observation was supported by ITC and calcein leakage data that indicated that these AMPs interact via very different mechanisms with anionic and zwitterionic LUVs [32,[44][45][46]. The enthalpy for the binding of these AMPs to pure POPC LUVs directly correlates to the length of side chain of the basic amino acid residues.…”

Antibacterial and anticancer activity of a series of novel peptides incorporating cyclic tetra-substituted Cα amino acids

“…65 Varying the distance (estimated distances are given in Table 4) between the polypeptide backbone and the positively charged side chain amine group defines three physicochemical properties 1) side chain molecular flexibility, defines the total 3D conformational space available to the AMP on binding to the surface of the bacterial membrane . 44 2) delocalization of the positive charge density of the side chain amine functionality, (We have shown using electrostatic surface potential maps the shorter the side chain, the closer the positive charge of the amine nitrogen comes to the partially negatively charged carbonyl oxygens of the peptide backbone. 66 Delocalization of electron density into the carbonyl oxygen of the amide bond, thus reduces the net positive charge on the side chain nitrogen atom.…”

“…44 Variations in total charge at the C-terminus can lead to selectivity for prokaryotic vs eukaryotic cells, as well as increased selectivity for specific bacterial strains. …”