Energetics and Partition of Two Cecropin-Melittin Hybrid Peptides to Model Membranes of Different Composition

Abstract

The energetics and partition of two hybrid peptides of cecropin A and melittin (CA(1-8)M(1-18) and CA(1-7)M(2-9)) with liposomes of different composition were studied by time-resolved fluorescence spectroscopy, isothermal titration calorimetry, and surface plasmon resonance. The study was carried out with large unilamellar vesicles of three different lipid compositions: 1,2-dimyristoil-sn-glycero-3-phosphocholine (DMPC), 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG), and a 3:1 binary mixture of DMPC/DMPG in a wide range of peptide/lipid ratios. The results are compatible with a model involving a strong electrostatic surface interaction between the peptides and the negatively charged liposomes, giving rise to aggregation and precipitation. A correlation is observed in the calorimetric experiments between the observed events and charge neutralization for negatively charged and mixed membranes. In the case of zwitterionic membranes, a very interesting case study was obtained with the smaller peptide, CA(1-7)M(2-9). The calorimetric results obtained for this peptide in a large range of peptide/lipid ratios can be interpreted on the basis of an initial and progressive surface coverage until a threshold concentration, where the orientation changes from parallel to perpendicular to the membrane, followed by pore formation and eventually membrane disruption. The importance of negatively charged lipids on the discrimination between bacterial and eukaryotic membranes is emphasized.

Covalent immobilization of antimicrobial peptides (AMPs) onto biomaterial surfaces

“…This can be ascribed to a first step of membrane surface coverage by the AMP until charge neutralization is reached. Thereafter, peptide orientation changes from parallel to perpendicular to the membrane surface, followed by pore formation and eventually membrane disruption [64][65][66].…”

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).…”

“…[8,9] Briefly, a known amount of the sample was submitted to acid hydrolysis in aqueous HCl 6 M containing 1 mM of aminobutyric acid as internal reference. The hydrolysis was carried out in a sealed glass tube at 100 C and over 24 h, for full cleavage of peptide bonds and concomitant quantitative release of the amino acids.…”

“…[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.…”

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.…”