Lysine-spermine conjugates: Hydrophobic polyamine amides as potent lipopolysaccharide sequestrants

Mark R. Burns, Stewart J. Wood, Kelly A. Miller, Thuan Nguyen, Jens R. Cromer, Sunil A. David

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are outer-membrane constituents of Gram-negative bacteria. Lipopolysaccharides play a key role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient. Therapeutic options aimed at limiting downstream systemic inflammatory processes by targeting lipopolysaccharide do not exist at the present time. We have defined the pharmacophore necessary for small molecules to specifically bind and neutralize LPS and, using animal models of sepsis, have shown that the sequestration of circulatory LPS by small molecules is a therapeutically viable strategy. In this paper, the interactions of a focused library of lysine-spermine conjugates with lipopolysaccharide (LPS) have been characterized. Lysine-spermine conjugates with the ε-amino terminus of the lysinyl moiety derivatized with long-chain aliphatic hydrophobic substituents in acyl or alkyl linkage bind and neutralize bacterial lipopolysaccharides, and may be of use in the prevention or treatment of endotoxic shock states.

Original languageEnglish (US)
Pages (from-to)2523-2536
Number of pages14
JournalBioorganic and Medicinal Chemistry
Issue number7
StatePublished - Apr 1 2005


  • Endotoxin
  • Lipopolysaccharide
  • Lysine-spermine conjugates
  • Sepsis


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