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Metallopeptide Catalysts for Structure-Selective Peptide/Protein Modification

Details

Project TitleMetallopeptide Catalysts for Structure-Selective Peptide/Protein Modification
Track Code2010-029
Short DescriptionNone
AbstractNone
 
Tagsmetallopeptide, protein modification, catalyst, biomolecules, antibody, rhodium, functionalization, Drug Conjugates, drug delivery
 
Posted DateSep 13, 2017 12:36 PM

Challenge

Selective modification of biomolecules is an important tool in the investigation of protein-protein interactions. Study of these interactions is important in understanding disease states and identifying and developing new therapies. Current protein modification protocols, however, are limited to targeting an amino acid type or rely on natural enzymatic processes that are difficult to manipulate. A robust chemical approach for the modification of a specific residue in a functional group-rich environment is therefore desired. 

Solution

The present invention describes a new method for the selective covalent modification of a specific amino acid residue in a peptide chain or protein domain. This targeted modification strategy is based on a combination of residue-selective, catalytic chemistry and secondary-structure recognition. 

The method involves the synthetic ligation of organometallic precursors to peptides. The resulting metallopeptides can bind to specific biological targets based on shape and deliver a selective catalyst to a specific functional group, thereby enabling selective, catalytic modification of the targeted side-chain. As a result of the catalytic nature of the recognition elements, this protocol is operational at the physiological concentrations of the targeted biomolecules. 

Benefits and Features

• Method is amenable to the modification of a wide range of amino acid residues 
• Method allows for covalent modification of natural and unnatural genetically-encoded polypeptide sequences 
• Optimization of method should allow for additional modes of reactivity 
• Localization-induced catalytic reactivity allows for low working concentrations of recognition elements 

Market Potential / Applications

Catalytic metallodrugs represent a relatively new class of drug candidates with a novel mode of action that includes selective recognition and irreversible inactivation of therapeutic targets. As a result, this invention might find application within the pharmaceutical and biotechnology industries in addition to being a new tool for fundamental investigation into biological processes. 

Development and Licensing Status

This method has proven successful for the covalent modification of a natural protein domain, and this modification can be achieved at different residues, depending on the metallopeptide structure.   Rice University scientists have developed a method to efficiently modify natural antibodies that can deliver drugs to target cells. 


Issued US patent 8,476,407 is available for licensing from Rice University.     

Rice Researcher

Zachary T. Ball is an assistant professor within the Department of Chemistry at Rice University. He is also associated with Rice University's Center for Biological and Environmental Nanotechnology and Smalley Institute, and his research interests include developing new methodologies in transition metal catalysis. 

Technology Relevant Papers and Web Links

Ball, Z.T. et al "Helix Induction by Dirhodium: Access to Biocompatible Metallopeptides with Defined Secondary Structure", Chem. Eur. J., 2010, 16, 6651-6659. 

Popp, B.V.; Ball, Z.T. "Structure-Selective Modification of Aromatic Side Chains with Dirhodium Metallopeptide Catalysts", J. Am. Chem. Soc. 2010, 132, 6660-6662. 

Popp, B.V.; Ball, Z.T. "Proximity-Driven Metallopeptide Catalysis: Remarkable Side-Chain Scope Enables Modification of the Fos bZip Domain", manuscript under review. 

Ohata, J., Ball, Z.T. "A Hexa-rhodium Metallopeptide Catalyst for Site-Specific Functionalization of Natural Antibodies", J. Am. Chem. Soc. 2017 139 (36), 12617-12622

Case #2010-029

Key Words: metallopeptide, protein modification, catalyst, biomolecules, antibody, functionalization, rhodium, drug conjugates, drug delivery

Inquiries to:

Andy Castillo, andy.castillo@rice.edu, (713) 348-2838