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One Step N-terminal Tagging of Endogenous Proteins for Therapeutic Delivery, Diagnostics, and In Vivo Imaging

Description:

N-Terminal Protein Modification Using Adenosine Substrates and Aminoacyl Transferase

 

Inventor

E. James Petersson, Associate Professor of Chemistry

 

Problem

The conjugation of synthetic molecules to the termini of proteins with minimal effects on protein folding and function is an active area of biochemical research.  Previous N-terminal protein modification methods suffer from side reaction products, incomplete specificity, low yields, and harsh organic solvent conditions.

 

Solution

Researchers in the Petersson lab have developed a minimal system for N-terminal protein labeling that uses an adenosine substrate of natural or unnatural amino acids and a single, readily available enzyme, aminoacyl tRNA transferase (AaT) from E. coli.  The use of aminoacyl adenosyl donors increases the substrate scope and reaction scale for N-terminal protein modification.  This process gives high yields of modified proteins under nondenaturing conditions to maintain natural protein folding and activity, while requiring only a single basic amino acid for specific recognition.  Furthermore, the reaction can be scaled to large quantities of protein because there is no reliance on purified tRNA as with fully enzymatic modification methods.

 

Advantages

•       Easily carry out N-terminal protein modification under conditions that maintain protein folding

•       Adenosine substrate readily synthesized from commercially available materials

•       No prior protein manipulation required, proteins can be obtained from any source

•       High yields, reaction can be driven to completion

•       Not limited by substrate specificity of aminoacyl tRNA synthetase

 

Applications

•       Reduce barriers to therapeutic and diagnostic uses of modified proteins

•       Deliver therapeutically active proteins

•       Immobilize proteins on surfaces

•       Modify proteins with chromophores or fluorophores for in vitro sensors

•       Tag proteins with in vivo imaging agents

 

Stage of Development

•       Proof-of-concept

 

Intellectual Property

USSN 9,376,700

 

Reference Media

Wagner AM et al.  Journal of the American Chemical Society, 2011, 133, 15139-15147.

Tanaka T et al.  Angewandte Chemie International Edition, 2013, 52, 6210-6213.

Wagner AM et al. Methods in Molecular Biology, 2015, 1337, 109-127.

 

Desired partnerships

•  License

Co-development

 

Transferase-mediated N-terminal protein modification

 

 

Download PDF

 

Docket #  X5991 


Patent Information:
For Information, Contact:
Joshua Jeanson
Associate Director, SEAS/SAS Licensing Group
University of Pennsylvania
jeanson@upenn.edu
Inventors:
E. James Petersson
Alan Saghatelian
Keywords:
Biotechnology