# US 2008/0188422 A1 · Ligands Having Metal Binding Ability and Targeting Properties > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2008/0188422 A1 - Document ID: US20080188422A1 - Status: Published application - Kind: A1 - Application number: 11/569,919 - Filed: 2005-06-01 - Published: 2008-08-07 - Earliest claimed: 2004-06-01 - Assignees: The Ohio State University Research Office of Technology Licensing & Commercialization - Inventors: James A. Cowan; Yan Jin; Seth Bradford; Nikhil Gokhale; Ada Cowan; Chun-An Chen - Web page: https://patentgrep.com/patent/US20080188422A1 ## CPC - A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 31/18: for HIV - A61P 37/00: Drugs for immunological or allergic disorders - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Ligands having a metal binding domain and a targeting domain are provided. The ligands can be used to target, inhibit, and catalytically degrade or inactivate a desired target. Methods of treating a disease or condition using the ligands are also provided. ## Claims ### Claim 1 A ligand comprising at least two separate domains wherein: one of the domains comprises a metal binding domain and one of the domains comprises a targeting domain targeted to a polynucleotide target, peptide target, or protein target; the metal binding domain is linked either directly to the targeting domain or by at least one linker; the ligand selectively degrades, inactivates, or inhibits the target via metal mediation; and the metal binding domain is selected from at least one of a modified or unmodified ATCUN motif, the PHGGGWGQ motif, a peptide motif having histidine as the first residue and glycine as the third residue from the N-terminus of the peptide motif; a peptide motif having histidine as the third residue from the N-terminus of the peptide motif, a zinc finger peptide having two cysteine and two histidine residues, a peptide conjugate with a synthetic metal binding motif, a peptide mimic, a cyclam, GGH, KGHK, VIHN, or YIHPF, ### Claim 4 (depends on 1) The ligand as claimed in claim 1 wherein the metal binding domain comprises a peptide. ### Claim 13 (depends on 1) The ligand as claimed in claim 1 wherein the targeting domain is selected from at least one peptide that binds to specific nucleic acids or proteins, at least one peptide that is a substrate for a protease, at least one peptide that is involved in the Renin-Angiotensin system, and antibodies. ### Claim 14 (depends on 1) The ligand as claimed in claim 1 wherein the targeting domain comprises captopril. ### Claim 15 (depends on 1) The ligand as claimed in claim 1 wherein the targeting domain comprises lisinopril. ### Claim 16 (depends on 1) The ligand as claimed in claim 1 wherein the targeting domain comprises Tat having a sequence of GRKKRRQRRRPPQ. ### Claim 17 (depends on 1) The ligand as claimed in claim 1 wherein the targeting domain comprises Rev having a sequence of TRQARRNRRRRWRERQR. ### Claim 18 (depends on 1) The ligand as claimed in claim 1 wherein the targeting domain comprises amino acids 1-20 of the hepatitis C virus core protein having a sequence of STNPKPQRKTKRNTNRRPQ. ### Claim 19 (depends on 1) The ligand as claimed in claim 1 wherein the targeting domain comprises Y-(D)-RFK, wherein (D) comprises a (D) configuration amino acid. ### Claim 20 (depends on 1) The ligand as claimed in claim 1 wherein the targeting domain comprises Thx having a sequence of MGKGDRRTRR GKIWRGTYGK YRPRKKK. ### Claim 21 (depends on 1) The ligand as claimed in claim 1 wherein the targeting domain comprises Staphylococcus aureus S8 residues 4-21 having a sequence of TDPIADMLTRVRNANMVR. ### Claim 22 (depends on 1) The ligand as claimed in claim 1 wherein the targeting domain comprises RSG which has a sequence of RRGSRPSGAERRRRAAAA. ### Claim 23 (depends on 1) The ligand as claimed in claim 1 wherein the targeting domain comprises residue 19-50 of the S15 protein of Thermus thermophilus having a sequence of GDTGSTEVQVALLTLRINRLSEHLKVHKKDHH. ### Claim 24 (depends on 1) The ligand as claimed in claim 1 having the sequence of GGHMGKGDRRTRRGKIWRGTYGKYRPRKKK. ### Claim 25 (depends on 1) The ligand as claimed in claim 1 having the sequence of GGHTRQARRNRRRRWRERQR. ### Claim 26 (depends on 1) The ligand as claimed in claim 1 having the sequence of GGHGTRQARRNRRRWRERQR. ### Claim 27 (depends on 1) The ligand as claimed in claim 1 having the sequence of GGHGGTRQARRNRRRRWRERQR. ### Claim 28 (depends on 1) The ligand as claimed in claim 1 having the sequence of GGHRRGSRPSGAERRRRAAAA. ### Claim 29 (depends on 1) The ligand as claimed in claim 1 having the structure ### Claim 30 (depends on 1) The ligand as claimed in claim 1 wherein a metal is bound to the metal binding domain. ### Claim 31 (depends on 30) The ligand as claimed in claim 30 wherein the metal comprises copper. ### Claim 32 (depends on 1, 30) The ligand as claimed in claims 1 and 30 wherein the ligand is a pharmaceutically acceptable basic salt. ### Claim 33 (depends on 1, 30) The ligand as claimed in claims 1 and 30 wherein the ligand is a pharmaceutically acceptable acidic salt. ### Claim 34 (depends on 1) The ligand as claimed in claim 1 wherein the metal binding domain is linked to the targeting domain by at least one glycine linker. ### Claim 35 (depends on 1) A pharmaceutical composition comprising at least one ligand according to claim 1 and at least one pharmaceutically acceptable excipient. ### Claim 36 (depends on 1) A method of treating a disease or condition in an animal comprising administering a therapeutically effective amount of at least one ligand comprising a ligand according to claim 1 wherein the ligand is selected to bind to and catalytically degrade or inactivate a target that is implicated in the particular disease or condition for which the ligand is being administered. ### Claim 37 (depends on 36) The method as claimed in claim 36 wherein the ligand further comprises a metal. ### Claim 38 (depends on 36) The method as claimed in claim 36 wherein the method further comprises binding a metal proximate the target prior to the ligand binding to the target. ### Claim 39 (depends on 36) The method as claimed in claim 36 wherein the animal is human. ### Claim 40 (depends on 36) The method as claimed in claim 36 wherein the therapeutically effective amount comprises an amount that is substoichiometric or sub-saturating in relation to the target. ### Claim 41 (depends on 36) The method as claimed in claim 36 wherein the disease is AIDS. ### Claim 42 (depends on 36) The method as claimed in claim 36 wherein the disease is cardiovascular disease. ### Claim 43 (depends on 36) The method as claimed in claim 36 wherein the condition is bacterial infection. ### Claim 44 (depends on 36) The method as claimed in claim 36 wherein the condition is hepatitis. ### Claim 45 (depends on 36) The method as claimed in claim 36 wherein the condition is diabetes. ### Claim 46 (depends on 36) The method as claimed in claim 36 wherein the condition is cancer. ### Claim 47 (depends on 36) The method as claimed in claim 36 wherein the condition is viral infection.