OLIGOMERIC PEPTIDES AND THEIR USE FOR THE TREATMENT OF HIV INFECTIONS.

摘要

The invention relates to oligomeric peptides with biological activity against HIV infection having the amino acid sequence (Z1-LE-X1-IP-X2-X3-X4-P-X5-X6-X7-X8- X9-X10-K-X11-X12-X13-X14-X15-Z2)n, wherein n indicates the number of monomeric peptide chains, whereby n is 2, 3 or 4; X1 is a lysine, alanine, or aspartic acid; X2 is a cysteine, methionine or isoleucine; X3 is a serine, cysteine, lysine or glycine; X4 is an isoleucine, alanine, phenylalanine or cysteine; X5 is a proline, D-proline or a substituted L-or D-proline; X6 is a cysteine or glutamic acid; X7 is an amino acid with a hydrophobic or an aromatic side chain or cysteine; X8 is an amino acid with a hydrophobic or an aromatic side chain or cysteine; Xg is an amino acid with an aromatic side chain; X1o is a glycine, alanine or asparagine; X11 is a proline, aspartic acid, octahydroindolyl-2-carboxylic acid or D-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; X12is a phenylalanine, alanine, glycine, glutamic acid or D-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; X13 is an amino acid with a hydrophobic or an aromatic side chain; X14is an amino acid with a hydrophobic or an aromatic side chain; X15 is a phenylalanine or deletion; Z1 is NH2 or a sequence of 1 to 10 amino acid residues; Z2 is COOH or a sequence of 1 to 10 amino acid residues; and oligomeric peptides which are fragments thereof and/or derivatives, especially amidated, alkylated, acylated, sulfated, pegylated, phosphorylated and/or glycosylated derivatives, and mutants thereof; and with the proviso that (a) if X12 is alanine, glycine, glutamic acid, or D-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid than X13, X14 and X15 are phenylalanine, valine and phenylalanine respectively; and/or (b) if X12 is phenylalanine, than X13, X14 and X15 are valine, phenylalanine and a deletion, respectively; and (c) there are at maximum three cysteine residues in a peptide; and (d) the oligomeric peptide has not the sequence (LEAIPCSIPPEFLFGKPFVF)2 (VIR-576); and (e) the monomeric peptide chains are not linked by peptide bonds between the N- terminus of one peptide chain to the C-terminus of another peptide chain.