Therapeutic peptide-based constructs

A pharmaceutical composition comprising a derivatized peptide-based construct of 8-15 amino acid moieties in length having heparin binding, heparin neutralizing, endothelial cell proliferation inhibiting, antiangiogenic, LPS binding, LPS neutralization, or antimicrobial properties comprising:

• a sequence having the formula:
• R1-α-χ-χ-α-χ-β-χ-α-R
• wherein,
• α is a hydrophilic basic amino acid moiety that is any one of lysine, arginine, histidine, ornithine, diaminobutyric acid, citrulline, or para-amino phenylalanine;
• β is a hydrophilic neutral amino acid moiety that is any one of asparagine, glutamine, serine, threonine, tyrosine, hydroxyproline, or 7-hydroxy-tetrahydroisoquinoline carboxylic acid;
• χ is a hydrophobic amino acid moiety that is any one of alanine, naphthylalanine, biphenylalanine, valine, leucine, isoleucine, proline, 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-naphthoic acid, γ-amino butyric acid, beta-alanine, difluorophenylalanine, fluorophenylalanine, nipecotic acid, α-aminobutyric acid, thienyl-alanine, or t-butyl-glycine;
• R is an amino acid moiety that is any one of -χ, -χ-α, -χ-α-χ, χ-α-χ-β, -χ-α-χ-β-χ, -χ-α-χ-β-χ-α, -χ-α-χ-β-χ-α-χ, -χ-α-χ-χ-α-χ, —NH2, -χ-NH2, -χ-α-NH2, -χ-α-χ-NH2, -χ-α-χ-β-NH2, -χ-α-χ-β-χ-NH2, -χ-α-χ-β-χ-α-NH2, -χ-α-χ-β-χ-α-χ-NH2, or -χ-α-χ-χ-α-χ-NH2;
• and
• wherein,
• R1 is any one of R2—CH2, R2—CH2—CO—, R2—CO—, R2—SO2, or R2—POz-;
• wherein,
• y=0−3,
• z=1−4;
• R2 is a hydrophobic moiety that is any one 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, or a functionalized heterocyclic molecule having at least 3 atoms, and
• a pharmaceutically acceptable diluent, adjuvant, or carrier.

A pharmaceutical composition comprising a composition of 8-15 amino acid moieties consecutively linked by peptide bonds, said composition having one or more heparin binding properties and comprising a sequence of the formula:

• R1-KLFR(naph-A)QAR3
• R1 is any one of R2—CH2, R2—CH2—CO—, R2—CO—, R2—SOy-, or R2 POz-;
• wherein,
• y=0−3,
• z=1−4;
• R2 is a hydrophobic moiety that is any one 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, or a functionalized heterocyclic molecule having at least three atoms;
• wherein R3 is any one of K, K(naph-A), K(naph-A)K, K(naph-A)KG, K(naph-A)KGS, K(naph-A)KGSI, K(naph-A)KGSIK or K(naph-A)KGSIKI;
• wherein the carboxyl terminal group is amidated or nonamidated,
• and, optionally, comprising at least one conservative substitution of amino acid moieties, and
• a pharmaceutically acceptable diluent, adjuvant, or carrier.