Structure-activity relationships of lipopolysaccharide sequestration in N-alkylpolyamines.

ABSTRACT: We have previously shown that simple N-acyl or N-alkyl polyamines bind to and sequester Gram-negative bacterial lipopolysaccharide, affording protection against lethality in animal models of endotoxicosis. Several iterative design-and-test cycles of SAR studies, including high-throughput screens, had converged on compounds with polyamine scaffolds which have been investigated extensively with reference to the number, position, and length of acyl or alkyl appendages. However, the polyamine backbone itself had not been explored sufficiently, and it was not known if incremental variations on the polymethylene spacing would affect LPS-binding and neutralization properties. We have now systematically explored the relationship between variously elongated spermidine [NH(2)-(CH(2))(3)-NH-(CH(2))(4

SUBMITTER: Shrestha A 

PROVIDER: S-EPMC3699868 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature