title: The effect of the placement and total charge of the basic amino acid clusters on antibacterial organism selectivity and potency.
abstract: Extensive circular dichroism, isothermal titration calorimetry and induced calcein leakage studies were conducted on a series of antimicrobial peptides (AMPs), with a varying number of Lys residues located at either the C-terminus or the N-terminus to gain insight into their effect on the mechanisms of binding with zwitterionic and anionic membrane model systems. Different CD spectra were observed for these AMPs in the presence of zwitterionic DPC and anionic SDS micelles indicating that they adopt different conformations on binding to the surfaces of zwitterionic and anionic membrane models. Different CD spectra were observed for these AMPs in the presence of zwitterionic POPC and anionic mixed 4:1 POPC/POPG LUVs and SUVs, indicating that they adopt very different conformations on interaction with these two types of LUVs and SUVs. In addition, ITC and calcein leakage data indicated that all the AMPs studied interact via very different mechanisms with anionic and zwitterionic LUVs. ITC data suggest these peptides interact primarily with the surface of zwitterionic LUVs while they insert into and form pores in anionic LUVs. CD studies indicated that these compounds adopt different conformations depending on the ratio of POPC to POPG lipids present in the liposome. There are detectable spectroscopic and thermodynamic differences between how each of these AMPs interacts with membranes, that is position and total charge density defines how these AMPs interact with specific membrane models and thus partially explain the resulting diversity of antibacterial activity of these compounds.
authors: Department of Chemistry, East Carolina University, Science and Technology, Suite 300, Greenville, NC 27858, USA.
authors: Amanda L
authors: AL
authors: Russell
authors: Anne M
authors: AM
authors: Spuches
authors: Brittany C
authors: BC
authors: Williams
authors: Divakaramenon
authors: D
authors: Venugopal
authors: David
authors: D
authors: Klapper
authors: Antoine H
authors: AH
authors: Srouji
authors: Rickey P
authors: RP
authors: Hicks
mesh_terms: D000595:Amino Acid Sequence; D024361:Amino Acids, Basic / Q000138:chemical synthesis*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry; D002151:Calorimetry; D002942:Circular Dichroism; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D024361:Amino Acids, Basic; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine