Patent ID: 6423825
Filing Date: 2002-07-23
Classification: A61K,C07K

Abstract:
A derivatized peptide-based construct of 8-15 amino acid moieties in length having heparin binding, heparin neutralizing, endothelial cell proliferation inhibiting, or antiangiogenic properties comprising:a sequence having the formula: R1-&agr;-&khgr;-&khgr;-&agr;-&khgr;-&bgr;-&khgr;-&agr;-R â€ƒwherein, R1 is selected from the group consisting of R2â€”CH2â€”, R2â€”CH2â€”COâ€”, R2â€”COâ€”, R2â€”SOyâ€”, and R2â€”POzâ€”; â€ƒwherein, y=0-3, z=1-4; R2 is a hydrophobic moiety selected from the group consisting of a cyclic molecule having at least 3 carbon atoms, a heterocyclic molecule having at least 3 atoms, a functionalized cyclic molecule having at least 3 carbon atoms, and a functionalized heterocyclic molecule having at least three atoms; wherein said R2 is a hydrophobic moiety selected from the group consisting of biotin, 2-biphenylene, 2-anthraquinone, 2-benzofuran, 2-indole, 1-isoquinoline, hydroxyphenyl, 2-quinoline, 1-[3-(3,4-dihydroxycinnamoyl)-1,3,4,5-tetrahydroxycyclohexane], 1-(3,5-dichloro-2-hydroxyphenyl), 1-(3,5-diiodo-2-hydroxyphenyl), 1-(3,5-dinitro-2-hydroxyphenyl), 1-(4-azido-2-hydroxyphenyl), 4-biphenyl, 2-biphenyl, 1-naphthyl, 2-naphthyl, 3-amino-2-naphthyl, 3-chloro-2-nitrophenyl, (3,4-dihydroxyphenyl), 3,4,5-trihydroxyphenyl, 2-chloro-3-nitrophenyl, 5-azido-2-nitrophenyl, 3-amino-2-pyrazine, 2-benzyloxycarbonyl-ethyl, 2-thiophene, 2-(3,4-dihydroxyphenyl)ethene, 5-bromo-3-indolemethylene, 2-(4-hydroxy-3-methoxyphenyl)ethene, 2-(3-chlorophenyl)ethene, 2-pyrazine, 4-imidazole, 2-imino-1-imidazolidine, pyridine, 3-piperidine, 4-piperidine, fluorescein, 2-(4-amino-3,5,6-trichloro-pyridine), and 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole; â€ƒwherein, &agr; is a hydrophilic basic amino acid moiety selected from the group consisting of lysine, arginine, histidine, ornithine, diaminobutyric acid, citrulline, and para-amino phenylalanine; &bgr; is a hydrophilic neutral amino acid moiety selected from the group consisting of asparagine, glutamine, serine, threonine, tyrosine, hydroxyproline, and 7-hydroxy-tetrahydroisoquinoline carboxylic acid; &khgr; is a hydrophobic amino acid moiety selected from the group consisting of alanine, naphthylalanine, biphenylalanine, valine, leucine, isoleucine, proline, hydroxyproline, phenylalanine, tryptophan, methionine, glycine, cyclohexylalanine, amino-isobutyric acid, norvaline, norleucine, tert-leucine, tetrahydroisoquinoline carboxylic acid, pipecolic acid, phenylglycine, homophenylalanine, cyclohexylglycine, dehydroleucine, 2, 2-diethylglycine, 1-amino-1-cyclopentane carboxylic acid, 1-amino-1-cyclohexane carboxylic acid, amino-benzoic acid, amino-naphthyl carboxylic acid, &ggr;-amino butyric acid, beta-alanine, difluorophenylalanine, fluorophenylalanine, nipecotic acid, aminobutyric acid, thienyl-alanine, and t-butyl-glycine; and R is an amino acid moiety selected from the group consisting of -&khgr;, -&khgr;-&agr;, -&khgr;-&agr;-&khgr;, &khgr;-&agr;-&khgr;-&bgr;, -&khgr;-&agr;-&khgr;-&bgr;-&khgr;, -&khgr;-&agr;-&khgr;-&bgr;-&khgr;-&agr;, -&khgr;-&agr;-&khgr;-&bgr;-&khgr;-&agr;-&khgr;, -&khgr;-&bgr;-&khgr;-&khgr;-&bgr;-&khgr;, â€”NH2, -&khgr;-NH2, -&khgr;-&agr;-NH2, -&khgr;-&agr;-&khgr;-NH2, -&khgr;-&agr;-&khgr;-&bgr;-NH2, -&khgr;-&agr;-&khgr;-&bgr;-&khgr;-NH2, -&khgr;-&agr;-&khgr;-&bgr;-&khgr;-&agr;-NH2, -&khgr;-&agr;-&khgr;-&bgr;-&khgr;-&agr;-&khgr;-NH2 and -&khgr;-&bgr;-&khgr;-&khgr;-&bgr;-&khgr;-NH2.