title: Poly-lysine peptidomimetics having potent antimicrobial activity without hemolytic activity.
abstract: Diversity of sequence and structure in naturally occurring antimicrobial peptides (AMPs) limits their intensive structure-activity relationship (SAR) study. In contrast, peptidomimetics have several advantages compared to naturally occurring peptide in terms of simple structure, convenient to analog synthesis, rapid elucidation of optimal physiochemical properties and low-cost synthesis. In search of short antimicrobial peptides using peptidomimetics, which provide facile access to identify the key factors involving in the destruction of pathogens through SAR study, a series of simple and short peptidomimetics consisting of multi-Lys residues and lipophilic moiety have been prepared and found to be active against several Gram-negative and Gram-positive bacteria containing methicillin-resistant Staphylococcus aureus (MRSA) without hemolytic activity. Based on the SAR studies, we found that hydrophobicity, +5 charges of multiple Lys residues, hydrocarbon tail lengths and cyclohexyl group were crucial for antimicrobial activity. Furthermore, membrane depolarization, dye leakage, inner membrane permeability and time-killing kinetics revealed that bacterial-killing mechanism of our peptidomimetics is different from the membrane-targeting AMPs (e. g. melittin and SMAP-29) and implied our peptidomimetics might kill bacteria via the intracellular-targeting mechanism as done by buforin-2.
authors: Division of Magnetic Resonance, Korea Basic Science Institute, 804-1 Yangchung-ri, Ochang, Chungbuk, 363-883, Republic of Korea.
authors: Mija
authors: M
authors: Ahn
authors: Binu
authors: B
authors: Jacob
authors: Pethaiah
authors: P
authors: Gunasekaran
authors: Ravichandran N
authors: RN
authors: Murugan
authors: Eun Kyoung
authors: EK
authors: Ryu
authors: Ga-hyang
authors: GH
authors: Lee
authors: Jae-Kyung
authors: JK
authors: Hyun
authors: Chaejoon
authors: C
authors: Cheong
authors: Nam-Hyung
authors: NH
authors: Kim
authors: Song Yub
authors: SY
authors: Shin
authors: Jeong Kyu
authors: JK
authors: Bang
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000254:growth & development*; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011107:Polylysine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D057786:Peptidomimetics; D011107:Polylysine