Concept explainers
Answers to all problems are at the end οΓthis book. Detailed solutions are available in the Student Solutions Manual. Study Guide, and Problems Book.
Characterizing a Covalent Enzyme Inhibitor Tosyl-L-phenylalanme cfaloromethyl
- Propose a mechanism for the inactivation reaction, indicating the structure of the produce(s).
- State why this inhibitor is specific tor cJiymotrypsin.
- Propose a reagent based on the structure of TPCK that might be an effective inhibitor of trypsin.
a.

To propose: The mechanism for the inactivation reaction which indicates the structure of the products.
Introduction:
Covalent enzyme inhibitor like TPCK is slowly reversible or totally irreversible. In many cases, these inhibitors are used to validate the pathway or target. There are targeted covalent enzyme inhibitors that have a slow offset, high binding efficiency as well as high potency to bind, increased selectivity decreased propensity for target-based drug resistance and prolonged pharmacodynamic effect.
Explanation of Solution
Chymotrypsin undergoes covalent inactivation reaction by nucleophilic attack on the
So, the mechanism of inactivation reaction is given below:
Hence, from the above discussion, it is clear that chymotrypsin undergoes covalent inhibition reaction.
b.

To propose: The reason for this inhibitor to be specific for chymotrypsin.
Introduction:
Covalent enzyme inhibitor like TPCK is slowly reversible or totally irreversible. In many cases, these inhibitors are used to validate the pathway or target. There are targeted covalent enzyme inhibitors that have a slow offset, high binding efficiency as well as high potency to bind, increased selectivity decreased propensity for target-based drug resistance and prolonged pharmacodynamic effects. Chymotrypsin plays an important part in the breakdown of proteins which is called proteolysis. The pancreas synthesizes the chymotrypsin. It cleaves the peptide amino bonds to digest the proteins.
Explanation of Solution
The inhibitor is chymotrypsin specific because the chloromethyl keto group reaches the active site by the hydrophobic reactions of chymotrypsin and the phenyl group of TPCK.
Hence, from the above discussion, it is clear that the inhibitor is chymotrypsin specific.
c.

To identify: A reagent that can be an effective inhibitor of Trypsin.
Introduction:
Chymotrypsin plays an important part in the breakdown of proteins which is called proteolysis. The pancreas synthesizes the chymotrypsin. It cleaves the peptide amino bonds to digest the proteins.
Explanation of Solution
The phenylalanine residue of TPCK has to be replaced with lysine or arginine to produce the specific reagents for the enzyme Trypsin.
Hence, from the above discussion, it is clear that the residual portion of TPCK only produces the specific reagent for Trypsin.
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Chapter 14 Solutions
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