Modification of cupredoxin derived peptides
View Patent ↗The present invention provides modified cupredoxin derived peptides with pharmacologic activity that have improved pharmacokinetic properties, and methods to use them to treat mammals suffering from various conditions related to the pharmacologic activities. Modifications of the cupredoxin derived peptides include amino acid sequence variants and structural derivations that increase the plasma half-life of the peptide, increase the specific activity of the pharmacologic activity, decrease immunogenicity, and decrease the biotransformation of the peptides. The modified cupredoxin derived peptides can be used in methods to treat mammals for cancer, conditions related to inappropriate angiogenesis, viral and bacterial infections, and specifically HIV and malaria, conditions related to ephrin signaling, and to deliver cargo compounds, including diagnostic compounds to cancer cell.
1. A peptide characterized by two or more lysine residues of the peptide being substituted with ε-(3,5-dinitrobenzoyl)-lysine residues in an i(i+4) spacing at amino acid residues equivalent to amino acid residues 53-56, 58-64 or 68-70 of SEQ ID NO: 1; and
the peptide being conjugated with a nanoparticle which is a noble metal.
2. The peptide of claim 1 , wherein the peptide consists of A SEQ ID NO: 45.
3. The isolated peptide of claim 1 , wherein the two or more modified lysine residues increase the stability of a least one α-helix.
4. A pharmaceutical composition, comprising the peptide of claim 1 and a pharmaceutically acceptable carrier.
5. The isolated peptide of claim 1 , wherein the noble metal is gold.
6. The peptide of claim 1 , which is conjugated with the nanoparticle via an electron transfer path.