Abstract
Both isomers of (E)-2,3-methanophenylalanine (▽EPhe), a sterically restricted amino acid, were incorporated into peptides in order to examine their possible enzyme inhibitory activity. Both (2R,3S)- and (2S,3R)-▽EPhe-Phe(or Leu)-OMe were found to inhibit effectively the hydrolysis of Ac-Tyr-OEt by chymotrypsin in a competitive manner. The ester groups of these dipeptides were quite resistant to chymotrypsin hydrolysis, and the ▽EPhe-Phe peptide bond was also entirely stable. The inhibition constant (Ki) of the most potent dipeptide of H-(2R,3S)-▽EPhe-Phe-OMe was 0.16 mM at 25°C. The inhibitory action of ▽Phe-containing peptides was found to depend on the configuration of the ▽Phe residue. The electrophilic nature of the cyclopropane ring which is conjugated with both the phenyl ring and the ester carbonyl group appears to be relevant to the inhibitory activity. Fully irreversible inactivation of chymotrypsin was achieved by its incubation with H-(2R,3S)-▽EPhe-Leu-OMe. An enzyme carboxylate group is thought to be responsible for nucleophilic attack on the cyclopropane ring leading to irreversible inactivation.
Original language | English |
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Pages (from-to) | 227-230 |
Number of pages | 4 |
Journal | FEBS Letters |
Volume | 250 |
Issue number | 2 |
DOIs | |
Publication status | Published - 1989 Jul 3 |
Externally published | Yes |
Keywords
- Amino acid isomer
- Enzyme inhibition
- Phenylalanine
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology