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TALF peptide-immunoglobulin G conjugates that bind lipopolysaccharide

Childrens' Service, Harvard Medical School, Boston, Massachusetts

Marek Kloczewiak

Creative Biomolecules, Hopkinton, Massachusetts, USA

Paul M. Loiselle

Childrens' Service, Harvard Medical School, Boston, Massachusetts

Steve F. Amato

Childrens' Service, Harvard Medical School, Boston, Massachusetts

Kerry M. Black

Childrens' Service, Harvard Medical School, Boston, Massachusetts

H. Shaw Warren

Childrens' Service, Harvard Medical School, Boston, Massachusetts, Department of Medicine, Shriners Burns Institute and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Several peptides mimicking the amino acid sequence of Tachypleus anti-LPS factor (TALF) bind LPS with high affinity and some neutralize LPS in vitro and in vivo (Kloczewiak M., Black K.M., Loiselle P., Cavaillon J-M., Wainwright N., Warren H.S. Synthetic peptides that mimic the binding site of horseshoe crab anti-lipopolysaccharide factor. J Infect Dis 1994; 170: 1490-1497). Two such peptides, TALF29-59 and TALF41-53, were covalently coupled to human IgG via a disulfide bond using the heterobifunctional linker, N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP). The resulting peptide-lgG conjugates contained 4-8 moles peptide per mole IgG and were evaluated for the ability to bind and neutralize LPS. Both conjugates bound LPS in a LPS capture Western blot assay. In a fluid-phase radioimmunoassay, half-maximal binding of 5 µg/ml LPS by many different Escherichia coli strains occurred at 50-100 µg/ml for both conjugates. Coagulation of Limulus amoebocyte lysate was only minimally inhibited by 5 µg/ml of each conjugate. Our data suggest that TALF peptide-lgG conjugates bind LPS with high affinity, but only weakly neutralize LPS. These studies provide an initial step towards the development of peptide-lgG preparations that might be useful for the treatment of Gram-negative sepsis by binding and clearing LPS.

Journal of Endotoxin Research, Vol. 3, No. 1, 49-55 (1996)
DOI: 10.1177/096805199600300106


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