Lipopolysaccharide Modulates Biological Activities of Human-β-Defensin Analogues but Not Non-Ribosomally Synthesized Peptides.

Human-β-defensins (HBD1-3) are antibacterial peptides containing three disulphide bonds. In the present study, the effect of lipopolysaccharide (LPS) on the antibacterial activities of HBD2-3, C-terminal analogues having a single disulphide bond, Phd1-3, and their corresponding myristoylated analogues MPhd1-3 were investigated. The effect of LPS on the activities of linear amphipathic peptides melittin, LL37 and non-ribosomally synthesized peptides, polymyxin B, alamethicin, gramicidin A, and gramicidin S was also examined.

Effects of increasing hydrophobicity by N-terminal myristoylation on the antibacterial and hemolytic activities of the C-terminal cationic segments of human-β-defensins 1-3.

Analogs of the cationic C-terminal segments of human-β-defensins HBD1-3, Phd1-3 with a single disulfide bond, exhibited comparable antimicrobial activity that was salt sensitive. They did not show hemolytic activity. In this study, N-terminal myristoylation was carried out on Phd1-3 to examine whether increasing hydrophobicity would result in improved antibacterial activity.

N-Terminal fatty acylation of peptides spanning the cationic C-terminal segment of bovine β-defensin-2 results in salt-resistant antibacterial activity.

Peptides spanning the C-terminal segment of bovine-β-defensin-2 (BNBD-2) rich in cationic amino acids, show antimicrobial activity. However, they exhibit considerably reduced activity at physiological concentration of NaCl. In the present study, we have investigated whether N-terminal acylation (acetylation and palmitoylation) of these peptides would result in improved antimicrobial activity.

Human-β-defensins-1-3 and analogs do not require proton motive force for antibacterial activity against Escherichia coli.

Human-β-defensins 1-3 (HBD-1-3) and their C-terminal analogs Phd-1-3 do not show antibacterial activity against Escherichia coli in the presence of mono- and divalent cations. Activity of peptides was examined against E. coli pretreated with carbonyl cyanide m-chlorophenylhydrazone (CCCP) and salt remedial Escherichia coli ftsEX, a deletion mutant of FtsEX complex [an ATP-binding cassette (ABC) transporter protein], in the presence of Na(+), Ca(2+), and Mg(2+).

Synthesis, conformational analysis and biological studies of cyclic cationic antimicrobial peptides containing sugar amino acids.

Sugar amino acid based 24-membered macrocyclic C2-symmetric cationic peptides were designed and synthesized. The cationic group was introduced in the sugar amino acids. The conformation of these cyclic compounds was ascertained through NMR techniques, which proved they were amphipathic in nature.

Antifungal activities of human beta-defensins HBD-1 to HBD-3 and their C-terminal analogs Phd1 to Phd3.

The activities of defensins HBD-1, HBD-2, and HBD-3 and their C-terminal analogs Phd1, Phd2, and Phd3 against Candida albicans were investigated. Phd1 to Phd3 showed lower-level activities than HBD-1 to HBD-3, although metabolic inhibitors did not render Phd1 to Phd3 inactive. Their activities were also less salt sensitive than those of HBD-1 to HBD-3.

Interaction of antibacterial peptides spanning the carboxy-terminal region of human beta-defensins 1-3 with phospholipids at the air-water interface and inner membrane of E. coli.

Synthetic peptides Phd1-3 spanning the cationic carboxy-terminal region of human beta-defensins HBD-1-3 have been shown to have antibacterial activity. Gross morphological changes were seen in E. coli cells treated with these peptides.

Antibacterial activities of synthetic peptides corresponding to the carboxy-terminal region of human beta-defensins 1-3.

The antibacterial activities of synthetic human beta-defensin analogs, constrained by a single disulfide bridge and in the reduced form, have been investigated. The peptides span the carboxy-terminal region of human beta-defensins (HBD-1-3), which have a majority of cationic residues present in the native defensins. The disulfide constrained peptides exhibited activity against Escherichia coli and Staphylococcus aureus whereas the reduced forms were active only against E.

Single disulfide and linear analogues corresponding to the carboxy-terminal segment of bovine beta-defensin-2: effects of introducing the beta-hairpin nucleating sequence d-pro-gly on antibacterial activity and Biophysical properties.

Mammalian defensins (alpha as well as beta forms) have a beta-hairpin structural motif spanning approximately 20 residues at the carboxy-terminal end. We have investigated the antibacterial activity and biophysical properties of synthetic peptides corresponding to the carboxy-terminal segment of bovine beta-defensin-2 (BNBD-2): VRNHVTC(1)RINRGFC(2)VPIRC(3)PGRTRQIGTC(4)FGPRIKC(5)C(6)RSW (positions of disulfide bonds are C(1)[bond]C(5), C(2)[bond]C(4), and C(3)[bond]C(6)). The parent sequence chosen was RCPGRTRQIGTIFGPRIKCRSW (P1), which spans the carboxy-terminal region of BNBD-2.