Ribonuclease zymogen design

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Hydrolase

Reexamination Certificate

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Reexamination Certificate

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07098016

ABSTRACT:
An enzyme is re-engineered to be a zymogen, an enzyme precursor which is converted into an enzyme by protease cleavage. In the example described here, an RNase A enzyme is converted into a zymogen by adding to the enzyme a bridge of amino acids linking the amino and carboxyl termini of the enzyme. The bridge has built in it a protease cleavage site for a specific protease, for example the protease plasmepsin II, produced by the malaria parasite. Since RNase A can be made cytotoxic, this permits a cytotoxic enzyme to be made in the form of a zymogen that becomes active only when it is acted on by a protease only present in a particular target cell such as a pathogen.

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