New antimicrobial cystatin C-based peptide active against gram-positive bacterial pathogens, including methicillin-resistant Staphylococcus aureus and multiresistant coagulase-negative staphylococci.
We describe the synthesis and antibacterial properties of a novel antimicrobial peptidyl derivative, (2S)-2-(Nalpha-benzyloxycarbonyl-arginyl-leucylamido-1-[(E)-cinnamoylamido]-3-methylbutane, structurally based upon the inhibitory centre of the human cysteine protease inhibitor, cystatin C. The derivative, here called Cystapep 1, displayed antibacterial activity against several clinically important gram-positive bacteria. It displayed minimal inhibitory and bactericidal concentrations of about 16 microg/ml for both Staphylococcus aureus and Streptococcus pyogenes. In radial agar diffusion assays, groups A, B, C and G streptococci as well as staphylococci were generally susceptible to the action of Cystapep 1, whereas pneumococci and enterococci were less susceptible. No activity against gram-negative bacteria was observed. Cystapep 1 also showed high activity against methicillin-resistant S. aureus (MRSA) and multiantibiotic-resistant coagulase-negative staphylococci (CNS), suggesting that its mechanism of action differs from those of most currently used antibiotics.
Jasir
Aftab
A
Department of Clinical Chemistry, University Hospital, Lund, Sweden.
Kasprzykowski
Franciszek
F
Kasprzykowska
Regina
R
Lindström
Veronica
V
Schalén
Claes
C
Grubb
Anders
A
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D055316:Cystatin C; D015891:Cystatins / Q000737:chemistry; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D006095:Gram-Positive Cocci / Q000187:drug effects*; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects
C481042:2-(N(alpha)-benzyloxycarbonyl-arginyl-leucylamido)-1-(cinnamoylamido)-3-methylbutane; D000900:Anti-Bacterial Agents; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D004151:Dipeptides; D009842:Oligopeptides