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dc.contributor.authorBalakrishna, Rajalakshmi
dc.contributor.authorWood, Stewart J.
dc.contributor.authorNguyen, Thuan B.
dc.contributor.authorMiller, Kelly A.
dc.contributor.authorKumar, E. V. K. Suresh
dc.contributor.authorDatta, Apurba
dc.contributor.authorDavid, Sunil A.
dc.date.accessioned2015-05-07T21:20:16Z
dc.date.available2015-05-07T21:20:16Z
dc.date.issued2006-03
dc.identifier.citationBalakrishna et. al. "Structural Correlates of Antibacterial and Membrane-Permeabilizing Activities in Acylpolyamines." Antimicrob. Agents Chemother. March 2006 vol. 50 no. 3 852-861 .

http://dx.doi.org/10.1128/AAC.50.3.852-861.2006
en_US
dc.identifier.urihttp://hdl.handle.net/1808/17654
dc.description.abstractA homologous series of mono- and bis-acyl polyamines with varying acyl chain lengths originally synthesized for the purpose of sequestering lipopolysaccharide were evaluated for antimicrobial activity to test the hypothesis that these bis-cationic amphipathic compounds may also bind to and permeabilize intact gram-negative bacterial membranes. Some compounds were found to possess significant antimicrobial activity, mediated via permeabilization of bacterial membranes. Structure-activity relationship studies revealed a strong dependence of the acyl chain length on antimicrobial potency and permeabilization activity. Homologated spermine, bis-acylated with C8 or C9 chains, was found to profoundly sensitize Escherichia coli to hydrophobic antibiotics such as rifampin. Nonspecific cytotoxicity is a potential drawback of these membranophilic compounds. However, the surface activity of these cationic amphipaths is strongly attenuated under physiological conditions via binding to serum albumin. Significant antibacterial activity is still retained in the presence of physiological concentrations of human serum albumin, suggesting that these compounds may serve as leads in the development of novel adjuncts to conventional antimicrobial chemotherapy.en_US
dc.description.sponsorshipThis work was supported by NIH grant 1R01 AI50107. We certify that there are no conflicts of interest. We thank an anonymous reviewer for insightful comments and suggestions.en_US
dc.publisherThe American Society for Microbiologyen_US
dc.titleStructural Correlates of Antibacterial and Membrane-Permeabilizing Activities in Acylpolyaminesen_US
dc.typeArticle
kusw.kuauthorBalakrishna, Rajalakshmi
kusw.kuauthorWood, Stewart J.
kusw.kuauthorNguyen, Thuan B.
kusw.kuauthorMiller, Kelly A.
kusw.kuauthorKumar, E. V. K. Suresh
kusw.kuauthorDatta, Apurba
kusw.kuauthorDavid, Sunil A.
kusw.kudepartmentDepartment of Medicinal Chemistryen_US
dc.identifier.doi10.1128/AAC.50.3.852-861.2006
kusw.oaversionScholarly/refereed, publisher version
kusw.oapolicyThis item does not meet KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


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