title: Characterization of antimicrobial, cytotoxic, and antiendotoxin properties of short peptides with different hydrophobic amino acids at "a" and "d" positions of a heptad repeat sequence.
abstract: To understand the influence of different hydrophobic amino acids at "a" and "d" positions of a heptad repeat sequence on antimicrobial, cytotoxic, and antiendotoxin properties, four 15-residue peptides with leucine (LRP), phenylalanine (FRP), valine (VRP), and alanine (ARP) residues at these positions were designed, synthesized, and characterized. Although valine is similarly hydrophobic to leucine and phenylalanine, VRP showed significantly lesser cytotoxicity than LRP and FRP; further, the replacement of leucines with valines at "a" and "d" positions of melittin-heptads drastically reduced its cytotoxicity. However, all four peptides exhibited significant antimicrobial activities that correlate well with their interactions with mammalian and bacterial cell membranes and the corresponding lipid vesicles. LRP most efficiently neutralized the LPS-induced pro-inflammatory mediators like NO, TNF-α, and IL-6 in macrophages followed by FRP, VRP, and ARP. The results could be useful for designing short antimicrobial and antiendotoxin peptides with understanding the basis of their activity.
authors: Molecular and Structural Biology Division, CSIR-Central Drug Research Institute , Lucknow 226 001, India.
authors: Sarfuddin
authors: S
authors: Azmi
authors: Saurabh
authors: S
authors: Srivastava
authors: Nripendra N
authors: NN
authors: Mishra
authors: Jitendra K
authors: JK
authors: Tripathi
authors: Praveen K
authors: PK
authors: Shukla
authors: Jimut Kanti
authors: JK
authors: Ghosh
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D004797:Enzyme-Linked Immunosorbent Assay; D005453:Fluorescence; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D020449:Repetitive Sequences, Amino Acid
chemical_list: D000596:Amino Acids; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D004731:Endotoxins; D010455:Peptides