Methods, Peptides and Antibodies for Preventing, Treating and Diagnosing an Inflammatory Condition

摘要

Provided is an isolated peptide or a peptidomimetic comprising a sequence corresponding to amino acid positions 431-616 or 411-616 of the human protein TLR4 or corresponding to amino acid positions 84-131 of the human protein MD-2. Provided is also an antibody with a specificity to an epitope that is a region corresponding to amino acid positions 411 to 616 of variant 1 the human protein TLR4. Provided is further an antibody with a specificity to an epitope that is a region corresponding to amino acid positions 86 to 131 of the human protein MD2. Provided is further the use of such antibody in the treatment or diagnosis of an inflammatory disorder. Also provided is an in-vitro method of identifying a compound capable of inhibiting the formation of a complex between one of the above peptides or whole molecules and an S100A8 or S100A9 or S100A8/S100A9 protein or a functional fragment thereof.

主权项

1. An isolated peptide or a peptidomimetic comprising at least one sequence selected from the group consisting of:
(i) the sequence of H(X1)26X2(X1)50E(X1)21X3(X1)48X4(X1)27X5CX6X1X1X7X8X9X10X11 (SEQ ID NO: 1), wherein X1 represents any amino acid, X2 represents one of histidine, glutamine and asparagine, X3 represents asparagine or lysine, X4 represents aspartic acid or glutamic acid, X5 represents glutamic acid, methionine or valine, X6 represents alanine, threonine, or lysine, X7 represents leucine or serine, X8 represents aspartic acid or asparagine, X9 represents one of lysine, arginine and methionine, X10 represents one of glutamine, glutamic acid, lysine, and arginine, and X11 represents glycine or aspartic acid, and (ii) the sequence of X24X1X20X21PX26X20(X1)31X20X29X1X23(X1)5X34 (SEQ ID NO: 6), wherein X20 represents a polar amino acid, X21 represents a nonpolar amino acid, X22 represents one of lysine, glutamic acid, methionine, leucine, threonine, and valine, X23 represents one of lysine, arginine, leucine, and isoleucine, X24 represents one of serine and threonine, X26 represents a nonpolar amino acid, lysine, aspartic acid or glutamic acid, X29 represents one of glycine and glutamic acid, and X34 represents tyrosine or histidine.