Methods of altering the binding affinity of a peptide to its receptor

• US 20040102381A1
• Filed: 11/19/2003
• Published: 05/27/2004
• Est. Priority Date: 08/14/1998
• Status: Abandoned Application

• Current Assignee: Biocon Limited (Biocon Incorporated)
• Original Assignee: Biocon Limited (Biocon Incorporated)
• Inventors: Anderson, Wesley R. Jr., Radhakrishnan, Balasingam, Ekwuribe, Nnochiri N., Price, Christopher H., Ansari, Aslam M.
• Application Number:
  US10/716,578
• Publication Number:
  US 20040102381A1
• Time in Patent Office: Days
• US Class Current: 514/12
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/02 of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
• CPC Class Codes: A61P 5/10 of the posterior pituitary hormones, e.g. oxytocin, ADH
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/18 of the parathyroid hormones

Abstract

The present invention relates to amphiphilic drug-oligomer conjugates capable of traversing the blood-brain barrier (“BBB”) and to methods of making and using such conjugates. An amphiphilic drug-oligomer conjugate comprises a therapeutic compound conjugated to an oligomer, wherein the oligomer comprises a lipophilic moiety coupled to a hydrophilic moiety. The conjugates of the invention further comprise therapeutic agents such as proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, etc., and prodrugs, precursors, derivatives and intermediates thereof, chemically coupled to amphiphilic oligomers.

Claims

1. A method for altering the binding affinity of a peptide to its receptor, comprising conjugating the peptide to an amphiphilic oligomer comprising a lipophilic moiety coupled to a hydrophilic moiety.

2. The method according to claim 1 further characterized in that the binding affinity is increased.

3. The method according to claim 1 further characterized in that the binding affinity is reduced.

4. The method of claim 1, wherein the peptide is a peptide or protein.

5. The method of claim 4, wherein the peptide is selected from the group consisting of:

enkephalin, adrenocorticotropic hormone, adenosine deaminase, ribonuclease, alkaline phosphatase, angiotensin, antibodies, arginase, arginine deaminease, asparaginase, caerulein, calcitonin, chemotrypsin, cholecystokinin, clotting factors, dynorphins, endorphins, enkephalins, erythropoietin, gastrin-releasing peptide, glucagon, hemoglobin, hypothalmic releasing factors, interferon, katacalcin, motilin, neuropeptide Y, neurotensin, non-naturally occurring opioids, oxytocin, papain, parathyroid hormone, prolactin, soluble CD-4, somatomedin, somatostatin, somatotropin, superoxide dismutase, thyroid stimulating hormone, tissue plasminogen activator, trypsin, vasopressin, and analogues and fragments of such peptides.

6. The method of claim 4 wherein the peptide is [met⁵]enkephalin.

7. The method of claim 1, wherein the lipophilic moiety is selected from the group consisting of fatty acids, C_1-26alkyls;

and cholesterol.

8. The method of claim 1, wherein the hydrophilic moiety is selected from the group consisting of sugars or PEG_1-7.

9. The method of claim 1, wherein the receptor is an opioid receptor.