Binaphthyl-based dicationic peptoids with therapeutic potential

Bremner, John B., Keller, Paul A., Pyne, Stephen G., Boyle, Timothy P., Brkic, Zinka, David, Dorothy M., Garas, Adel, Morgan, Jody, Robertson, Mark, Somphol, Kittiya, Miller, Michael H., Howe, Adam S., Ambrose, Paul, Bhavnani, Sujata, Fritsche, Thomas R., Biedenbach, Douglas J., Jones, Ronald N., Buckheit, Robert W., Watson, Karen M., Baylis, Dean, Coates, Jonathan A., Deadman, John, Jeevarajah, Dharshini, McCracken, Andrea, and Rhodes, David I. (2010) Binaphthyl-based dicationic peptoids with therapeutic potential. Angewandte Chemie International Edition, 49 (3). pp. 537-540.

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[Extract] While the cationic glycopeptide vancomycin has long been regarded as the gold standard for the treatment of recalcitrant Gram-positive bacterial infection, this position has been compromised by the emergence of resistant strains. The first report of such resistance emerged in 1988, and has subsequently widened amongst the enterococci and staphylococci, including methicillin-resistant Staphylococcus aureus (MRSA); 1, 2 cross-resistance to linezolid is also a concern. Some recent chemical strategies for overcoming this resistance have centered on other high molecular weight cyclic peptides, elegantly crafted vancomycin11 or vancomycin aglycone analogues, potent dual-action vancomycin/β-lactam hybrid antibiotics,or large vancomycin dimers. An alternative strategy is to design smaller, simpler cationic peptoids with some related design features to vancomycin which could still interact with the altered peptide-glycan cell-wall moiety in both vancomycin-resistant and -sensitive strains and thus broaden the antibacterial spectrum. Svendsen et al. designed minimal cationic peptidomimetics, and a pharmacophore has been developed for dipeptides which includes the presence of two cationic charges and two hydrophobic units of steric bulk. Subsequently, cationic tripeptide analogues were developed that demonstrated good activity against both Gram-positive (including MRSA) and Gram-negative bacteria, but were not evaluated with respect to vancomycin-resistant strains.

Item ID: 36824
Item Type: Article (Research - C1)
ISSN: 1521-3773
Keywords: antibiotics, biological activity, bioorganic chemistry, drug discovery, peptidomimetics
Date Deposited: 10 Dec 2014 07:31
FoR Codes: 03 CHEMICAL SCIENCES > 0305 Organic Chemistry > 030503 Organic Chemical Synthesis @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
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