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 of TALF 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 TALF or other LPS-binding proteins may be useful for the design of drugs for treatment of endotoxemia.
Kloczewiak
M
M
Department of Surgery, Shriners Burns Institute, Massachusetts General Hospital, Boston.
Black
K M
KM
Loiselle
P
P
Cavaillon
J M
JM
Wainwright
N
N
Warren
H S
HS
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D001665:Binding Sites; D016207:Cytokines / Q000096:biosynthesis; D003609:Dactinomycin; D006737:Horseshoe Crabs / Q000737:chemistry*; D006801:Humans; D007447:Invertebrate Hormones / Q000302:isolation & purification / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000633:toxicity; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D009500:Neutralization Tests; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D016207:Cytokines; D007447:Invertebrate Hormones; D008070:Lipopolysaccharides; D010455:Peptides; C034705:antilipopolysaccharide factor (Limulus); D003609:Dactinomycin