Anti-Cancer Drug Research with Purified P-glycoprotein

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Researchers
Ina Urbatsch
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David McClure
Director Licensing 806-834-5899
David Snow
Director Intellectual Property 806-834-4989
Patent Protection

Methods and composition to enhance production of fully functional p-glycoprotein in pichia pastoris

US Patent Pending US 20130011909 A1
Files and Attachments
P-glycoprotein Multi-drug Resistance Protein Manuscript [PDF]
Drug-Resistant P-glycoprotein Purity and Yield for Anti-Cancer Drugs [PDF]

P-glycoprotein is Critical for Anti-Cancer Drug and Other Pharmaceutical Research

Anti-cancer and other drug therapies are affected by the multi-drug resistant protein P-glycoprotein. Research of the drug is critical to determine its role in allowing anti-cancer drugs and other drug therapies to target diseases in the body.

P-glycoprotein is a plasma-membrane protein that actively extrude anti-cancer agents from the cell interior, decreasing drug accumulation and thus allowing the multidrug-resistant cells to survive in the presence of toxic levels of chemotherapeutic agents.

This method for creating high-quality amounts of the multi-drug resistant protein P-glycoprotein produces three times the volume that other methods do. 

P-glycoprotein Research Prevents Anti-Cancer and Other Drug Resistance

P-glycoprotein, which occurs naturally in the human body, is a plasma membrane protein that pumps a wide range of hydrophobic (non-water soluble) compounds out of cells. P-glycoprotein likely evolved in humans as a defense mechanism to flush harmful substances out of the body’s cells.

Unfortunately, this defensive function has a substantial downside. In chemotherapy, for example, P-glycoprotein prevents the accumulation of many anti-cancer drugs.  If these drugs don’t reach their target, tumors can grow unchecked and become drug-resistant. 

P-glycoprotein also prevents effective drug treatment for HIV, epilepsy, Alzheimer’s, and various psychiatric illnesses.  Science still has work to do to fully understand the interaction of P-glycoprotein with drugs, inhibitors, and the molecular mechanism of drug export. The large-scale production of the fully functional protein is essential for these endeavors. 

Pure P-glycoprotein Production through Codon Optimization

This process for creating higher yields of pure P-glycoprotein uses codon optimization, a technique for improving the protein expression in living organisms by manipulating its genes. The result is a three-fold higher yield of pure protein from the optimized P-glycoprotein (Opti-Pgp) with a quality similar to or better than wild-type P-glycoprotein.

Pichia Pastoris yeast is the medium used to grow the protein. P Pastoris is a cost-effective expression system that provides a high biomass of yeast cells in fermentor cultures and, thus, greater amounts of protein per culture volume than any other expression system. The significantly higher yields of protein in the native folded state, its higher purity, and improved functional capacity establish the value of using highly expressed genes in the yeast P. pastoris; and provide a basis to improve production of other membrane proteins.

Applications

  • Biotech companies
  • Pharmaceutical companies working on multi-drug resistant cancers
  • Research and treatment of HIV, epilepsy, Alzheimer’s, and other psychiatric illnesses
  • University biotech or health research centers 

Advantages

  • Method produces large, high-quality, quantities of purified P-glycoprotein
  • Pichia Pastoris provides low-cost expression system to grow protein
  • Protein remains in its native folded state
  • Provides the basis to improve production of other membrane proteins