Interaction and Lipid-Induced Conformation of Two Cecropin−Melittin Hybrid Peptides Depend on Peptide and Membrane Composition

Abstract

The interaction of two hybrid peptides of cecropin A and melittin [CA(1-8)M(1-18) and CA(1-7)M(2-9)] with liposomes was studied by differential scanning calorimetry (DSC), circular dichroism (CD), and quasi-elastic light scattering (QELS). The study was carried out with large unilamellar vesicles (LUVs) of three different lipid compositions: 1,2-dimyristoil-sn-glycero-3-phosphocholine (DMPC), 1,2-dimyristoylsn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and a binary mixture of DMPC/DMPG, in a wide range of peptide-to-lipid (P:L) molar ratios (0 to 1:7). DSC results indicate that, for both peptides, the interaction depends on membrane composition, with very different behavior for zwitterionic and anionic membranes. CD data show that, although the two peptides have different secondary structures in buffer (random coil for CA(1-7)M(2-9) and predominantly -sheet for CA(1-8)M(1-18)), they both adopt an R-helical structure in the presence of the membranes. Overall, results are compatible with a model involving a strong electrostatic surface interaction between the peptides and the negatively charged liposomes, which gives place to aggregation in the gel phase and precipitation after a threshold peptide concentration. In the case of zwitterionic membranes, a progressive surface coverage with peptide molecules destabilizes the membrane, eventually leading to membrane disruption. Moreover, delicate modulations in behavior were observed depending on the peptide.

Facile Regioselective Synthesis of a Novel Chitosan–Pexiganan Conjugate with Potential Interest for the Treatment of Infected Skin Lesions

“…[8,9] The target peptide was isolated from the crude mixture by preparative HPLC and characterized by analytical HPLC, AAA, and MALDI-TOF MS (data not shown).…”

“…[6] This was followed by the latest (as of 13 March 2008) press release on new phase III clinical trials promoted by this company that confirm the efficacy of pexiganan to be statistically equivalent to that of oral antibiotic therapy. [7] Taking advantage of our prior experience in the synthesis and study of antimicrobial peptides, [8][9][10] as well as in the development of novel chitosan-based biopolymers for biomedical applications, [11][12][13] we decided to break through to the preparation of a novel chitosan-pexiganan conjugate with potential application in the topical treatment of infected diabetic foot ulcers. We hope such a conjugate will combine the excellent antimicrobial properties of pexiganan with the well-known biocompatibility and skin-injury-healing ability of chitosan.…”

Dynamics of an antibiotic oligopeptide

“…This hybrid oligopeptide, called CM15 in the following, is a prominent member of a family of eukaryotic antimicrobial peptides which are being studied intensely by a variety of techniques to optimise potency and specificity, focusing in particular on their membrane interactions [5,6]. CM15 is a hybrid comprising seven amino acid residues from cecro/pin A and eight from mellitin: CA(1-7)M(2-9), with sequence H-KWKLFKK-IGAVLKVL-NH 2 .…”

Hydration water and peptide dynamics – two sides of a coin. A neutron scattering and adiabatic calorimetry study at low hydration and cryogenic temperatures

“…One particularly successful member of this family is CA(1-7)M(2-9), which we have been studying by a variety of biophysical methods. 55,56 The peptide has a random structure in aqueous solution, and acquires an a-helix secondary structure in the presence of membranes.…”