SYNTHETIC PEPTIDES THAT MIMIC THE BINDING-SITE OF HORSESHOE-CRAB ANTILIPOPOLYSACCHARIDE FACTOR

Tachypleus antilipopolysaccharide (LPS) factor (TALF) is a protein of 102 amino acids in the lysate of amebocytes of Tachypleus tridentatus that binds bacterial LPS with high affinity and blocks its biologic ac tivity in numerous assays. To elucidate the minimal sequences that bin d LPS, overlapping synthetic peptides based on the sequence of TALF we re assessed for the ability to bind and neutralize LPS. TALF41-53 was the minimal sequence that bound LPS, as assessed by a slot blot captur e assay. TALF29-59 bound LPS with the highest potency. TALF29-59 decre ased LPS-induced coagulation of limulus amebocyte lysate, induction of cytokines from human monocytes, and LPS-induced lethality in sensitiz ed mice. Synthetic peptides based on TALF or other LPS-binding protein s may be useful for the design of drugs for treatment of endotoxemia.