Hormone-Receptor Interactions. Carboranylalanine (Car) as a Phenylalanine Analogue: Reactions with Chymotrypsin
✍ Scribed by Walter Fischli; Othmar Leukart; Robert Schwyzer
- Publisher
- John Wiley and Sons
- Year
- 1977
- Tongue
- German
- Weight
- 301 KB
- Volume
- 60
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Abstract
In order to test the effects of the replacement of phenylalanine by carboranylalanine (Car) in biological ligand‐acceptor interactions, Z · Ala‐Ala‐Car · OH (1) and Ac · Car · OEt (2) were synthesized and their reactions with chymotrypsin studied. The two compounds proved to be good inhibitors with K(i) values of 3 · 10^−4^M (1) and 8.6 · 10^4^M (2); the K(i) of Z · Ala‐Ala‐Phe · OH (1a) is 1 · 10^−3^M. The inhibition constants were determined by a new photolytic technique, inhibition of photoaffinity labelling by Z · Ala‐Ala‐Phe(__p__N~3~) · OH. Ac · Car · OEt is not hydrolysed by chymotrypsin. The findings indicate that the carboranyl group can interact with the ‘phenyl recognition site’ of the enzyme to produce the binding that is characteristic of aromatic amino acid residues. However, some kind of distortion in the region of the ‘mechanistic site’ must be postulated in order to account for the failure of hydrolysis. Some possible effects of the replacement of aromatic amino acids by Car in peptide hormones on hormone‐receptor interactions are discussed.