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 activity in numerous assays. To elucidate the minimal sequences that bind LPS, overlapping synthetic peptides based on the sequence ofTALF were assessed for the ability to bind and neutralize LPS. TALF41-53 was the minimal sequence that bound LPS, as assessed by a slot blot capture assay. TALF29-59 bound LPS with the highest potency. TALF29-59 decreased LPS-induced coagulation of limulus amebocyte lysate, induction of cytokines from human monocytes, and LPS-induced lethality in sensitized mice. Synthetic peptides based on T ALF or other LPS-binding proteins may be useful for the design of drugs for treatment of endotoxemia. Endotoxin (lipopolysaccharide [LPS]) from gram-negative bacteria induces the amebocytes of horseshoe crabs to aggre-gate and degranulate. Presumably, this clotting reaction rep-resents an important defense used by horseshoe crabs against invasion ofgram-negative bacteria. The proteins responsibl