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., Cavaillo
n J-M., Wainwright N., Warren H.S. Synthetic peptides that mimic the b
inding 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)propionat
e (SPDP). The resulting peptide-IgG conjugates contained 4-8 moles pep
tide per mole IgG and were evaluated for the ability to bind and neutr
alize LPS. Both conjugates bound LPS in a LPS capture Western blot ass
ay. In a fluid-phase radioimmunoassay, half-maximal binding of 5 mu g/
ml LPS by many different Escherichia coli strains occurred at 50-100 m
u g/ml for both conjugates. Coagulation of Limulus amoebocyte lysate w
as only minimally inhibited by 5 mu g/ml of each conjugate. Our data s
uggest that TALF peptide-IgG conjugates bind LPS with high affinity, b
ut only weakly neutralize LPS. These studies provide an initial step t
owards the development of peptide-IgG preparations that might be usefu
l for the treatment of Gram-negative sepsis by binding and clearing LP
S.