Steric Enhancement of Imidazole Basicity incis-Urocanic Acid Derivatives: Models for the Action of Chymotrypsin
✍ Scribed by Mary J. Cloninger; Perry A. Frey
- Book ID
- 102564955
- Publisher
- Elsevier Science
- Year
- 1998
- Tongue
- English
- Weight
- 223 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0045-2068
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✦ Synopsis
To test the hypothesis that substrate-induced steric compression between His 57 and Asp 102 at the active site of chymotrypsin can increase the basicity of His 57, we have synthesized the cis-and trans-isomers of 2-bromo-3-(N-tritylimidazole)-2-propenoic acid and 2-chloro-3-(N-tritylimidazole)-2-propenoic acid and compared selected properties with those of cis-and trans-urocanic acids. The cis-isomers display low field 1 H NMR signals at 17 ppm in dimethylsulfoxide, similar to cis-urocanic acid; whereas the trans-isomers do not show strong hydrogen bonds. Increasing the size of the C2 substituent (H Ͻ Cl Ͻ Br) in the cis-isomers increases the pK a of the imidazolium group from 6.78 for H to 7.81 and 9.10 for Cl and Br, respectively; whereas the pK a s of the trans isomers are all 6.0 Ϯ 0.1. The results indicate that the cis-urocanic acid derivatives with large substituents at C2 act as proton sponges in water, and they support the concept that steric compression in the catalytic triad of chymotrypsin can increase the basicity of His 57.