Ab initio design of potent anti-MRSA peptides based on database filtering technology

Biswajit Mishra, Guangshun Wang

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

To meet the challenge of antibiotic resistance worldwide, a new generation of antimicrobials must be developed.(1) This communication demonstrates ab initio design of potent peptides against methicillin-resistant Staphylococcus aureus (MRSA). Our idea is that the peptide is very likely to be active when the most probable parameters are utilized in each step of the design. We derived the most probable parameters (e.g., amino acid composition, peptide hydrophobic content, and net charge) from the antimicrobial peptide database(2) by developing a database filtering technology (DFT). Different from classic cationic antimicrobial peptides usually with high cationicity, DFTamP1, the first anti-MRSA peptide designed using this technology, is a short peptide with high hydrophobicity but low cationicity. Such a molecular design made the peptide highly potent. Indeed, the peptide caused bacterial surface damage and killed community-associated MRSA USA300 in 60 min. Structural determination of DFTamP1 by NMR spectroscopy revealed a broad hydrophobic surface, providing a basis for its potency against MRSA known to deploy positively charged moieties on the surface as a mechanism for resistance. Our ab initio design combined with database screening(3) led to yet another peptide with enhanced potency. Because of the simple composition, short length, stability to proteases, and membrane targeting, the designed peptides are attractive leads for developing novel anti-MRSA therapeutics. Our database-derived design concept can be applied to the design of peptide mimicries to combat MRSA as well.

Original languageEnglish (US)
Pages (from-to)12426-12429
Number of pages4
JournalJournal of the American Chemical Society
Volume134
Issue number30
DOIs
StatePublished - Aug 1 2012

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Methicillin
Methicillin-Resistant Staphylococcus aureus
Peptides
Databases
Technology
Antimicrobial Cationic Peptides
Hydrophobicity
Microbial Drug Resistance
Chemical analysis
Hydrophobic and Hydrophilic Interactions
Antibiotics
Nuclear magnetic resonance spectroscopy
Screening
Peptide Hydrolases
Amino acids
Magnetic Resonance Spectroscopy
Anti-Bacterial Agents
Membranes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Ab initio design of potent anti-MRSA peptides based on database filtering technology. / Mishra, Biswajit; Wang, Guangshun.

In: Journal of the American Chemical Society, Vol. 134, No. 30, 01.08.2012, p. 12426-12429.

Research output: Contribution to journalArticle

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