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A General Method for Insertion of Functional Proteins within Proteins via Combinatorial Selection of Permissive Junctions. | LitMetric

AI Article Synopsis

  • * The study introduces a method that utilizes a large library of varied N- and C-terminal junctions along with a powerful selection system focused on functionality.
  • * Successful integration of the full Leptin and follicle-stimulating hormone (FSH) into an antibody was achieved, demonstrating the potential of this method for developing novel therapeutic proteins with retained activity.

Article Abstract

A major goal of modern protein chemistry is to create new proteins with different functions. One approach is to amalgamate secondary and tertiary structures from different proteins. This is difficult for several reasons, not the least of which is the fact that the junctions between secondary and tertiary structures are not degenerate and usually affect the function and folding of the entire complex. Here, we offer a solution to this problem by coupling a large combinatorial library of about 10(7) different N- and C-terminal junctions to a powerful system that selects for function. Using this approach, the entire Leptin and follicle-stimulating hormone (FSH) were inserted into an antibody. Complexes with full retention of function in vivo and in vitro, although rare, were found easily by using an autocrine selection system to search for hormonal activity. Such large diversity systems, when coupled to robust selection systems, should enable construction of novel therapeutic proteins.

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Source
http://dx.doi.org/10.1016/j.chembiol.2015.07.011DOI Listing

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