Chaperonin Partitioning System for Misfolding Proteins

Technology ID: 06KUMC018

Description:  Since there are a growing number of protein folding diseases that result from an intrinsic destabilization of a particular folded native state toward partially folded states, the utility of an immobilized GroEL chaperonin "sink" method will allow us to identify ligands that will stabilize the native state, thereby preventing the formation of aggregation prone partially unfolded states.  Specifically, this feasible high-throughput screening system works by identifying potential ligand candidates that PREVENT the transient misfolded intermediate of the target protein from binding to the high affinity chaperonin and thereby increasing the amount of soluble protein in the particular test solution.  Thus, the measurable parameter in the chaperonin sink will be a simple quantitation of the soluble protein product.  Once identified, the potential ligand/drug can be tested or further developed in vitro and in vivo to eventually provide a clinically useful compound to prevent protein folding diseases.  Work in this laboratory has already demonstrated the feasibility of using this approach with non-disease protein partitioning reaction involving the chaperonin substrate mitochondrial rhodanese. 

Faculty members at the KUMC have developed an in vitro process that can rapidly and easily screen through many commercial and public chemical libraries to identify small molecule native state stabilizers that prevent protein misfolding and aggregation.  The method of screening is applicable in solving a wide array of protein folding diseases and protein binding states.

Patent: N/A

Specific Market:  This folding system will enable researchers to determine if misfolding proteins can be properly folded, which is the most crucial first step in developing small molecule therapeutics to combat protein folding diseases.

Market Size: N/A

Stage of Development:  The inventors have tested this system with proteins that kinetically partitioned between folded and misfolded states.  They have demonstrated the stabilizing the particular protein against misfolding prevents the partitioning reaction from occurring.

Benefits: This partitioning method can be controlled and appears to be much more rapid than systems that are allowed to equilibrate (don't prevent refolding reaction).

Publications:  Smith K.S., Voziyan P.A. and Fisher M.T., (1998) Partitioning of rhodanese into Gro EL chaperonin binds a reversibly oxidized form derived from the native protein, The Journal of Biological Chemistry 273, 28677-28681.

Confidential Disclosure Agreement:  KUMC is willing to enter into a CDA for the purpose of negotiating a License Agreement.  If you are interested in learning details of this invention, please contact the Technology
Transfer Office at 913-588-5721.