ANALOGUES OF LIPOPOLYSACCHARIDE-BINDING PROTEIN (LBP)-DERIVED PEPTIDES THAT EFFICIENTLY NEUTRALIZE LIPOPOLYSACCHARIDES (LPS)

摘要

The invention provides an LPS-binding and -neutralizing peptidecomprising the amino acid sequence X-1-2-3-4-5-6-7-8-9-10-11-12-13-14-Y,wherein:X is a linear chain from zero to four amino acids.(1) is one of the amino acids alanine, threonine, glutamine, asparagine orserine; and if and only if at least one of the a.a. at positions +5, +9, +10,+11 or+13 has been replaced (from the native LBP sequence) according to what isherein described, then (1) could also be arginine or lysine.(2) is one of the amino acids alanine, valine, isoleucine, leucine,phenylalanine,methionine, tryptophan or tyrosine.(3) is one of the amino acids glutamine, asparagine, serine or threonine.(4) is one of the amino acids glycine, alanine, valine, isoleucine, leucine,phenylalanine, methionine, tryptophan or tyrosine.(5) is one of the amino acids alanine, threonine, glutamine, asparagine orserine; and if and only if at least one of the a.a. at positions +1, t9, t10,+11or +13 has been replaced according to what is herein described, then (5) couldalso be arginine or lysine.(6) is one of the amino acids tryptophan or phenylalanine.(7) is one of the amino acids lysine or arginine.(8) is one of the amino acids alanine, valine, isoleucine, leucine,phenylalanineor tyrosine.(9) is one of the amino acids alanine, threonine, glutamine, asparagine orserine; and if and only if at least one of the a.a. at positions +1, +5, +10,+11or +13 has been replaced according to what is herein described, then (9) couldalso be arginine or lysine.(10) is one of the amino acids alanine, valine, isoleucine, leucine,phenylalanine, methionine, tryptophan or tyrosine; and if and only if at leastone of the a.a. at positions +1, +5, +g, +11 6 +13 has been replaced accordingto what is herein described, then (10) could also be lysine or arginine.(11) is one of the amino acids alanine or valine; and if and only if at leastone ofthe a.a. at positions +1, +5, +g, +10, o +13 has been replaced according towhat is herein described, then (11) could also be serine; and if and only ifthea.a. at position +10 has bean replaced according to what is herein described,then (11) could also be threonine, glutamine, asparagine, lysine or arginine.(12) is one of the amino acids phenylalanine, tryptophan or tyrosine.(13) is one of the amino acids alanine, threonine, glutamine, asparagine orserine; and if and only if at least one of the a.a. at positions +1, +5, +9,+10 o+11 has been replaced according to what is herein described, then (13) couldalso be phenylalanine, arginine or lysine; and if and only if the a.a atposition+14 is lysine or arginine, then (13) could also be glycine.(14) is one of the amino acids lysine, arginine or alanine, and if and only ifthea.a. at position t13 has been replaced according to what is herein described,then (14) could also be valine, isoleucine, leucine, phenylalanine,methionine,tryptophan or tyrosine.