Functionalized dendrimers as endotoxin sponges

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

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are outer-membrane constituents of Gram-negative bacteria, and play a key role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient. We had previously 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. Polyamidoamine dendrimers, with the surface amines substoichiometrically derivatized with alkyl groups bind LPS with high affinity, neutralize LPS-induced inflammatory responses in vitro, and afford protection in a murine model of endotoxic shock. Dendrimers represent a new class of potentially useful compounds for the therapy of Gram-negative sepsis.

Original languageEnglish (US)
Pages (from-to)1295-1298
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume15
Issue number5
DOIs
StatePublished - Mar 1 2005

Bibliographical note

Funding Information:
This work was supported from NIH grants 5U01AI-056476, 1R01 AI50107, and a First Award Grant from P20 RR015563 from the COBRE Program of the National Center for Research Resources and matching support from the State of Kansas, and the University of Kansas.

Keywords

  • Dendrimers
  • Endotoxin
  • Lipopolysaccharide
  • Sepsis

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