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Abstract
The trans-epoxysuccinyl amide group as a biologically active moiety in cysteine protease inhibitors such as loxistatin acid E64c has been used as a benchmark system for theoretical studies of environmental effects on the electron density of small active ingredients in relation to their biological activity. Here, the synthesis and the electronic properties of the smallest possible active site model compound are reported to close the gap between the unknown experimental electron density of trans-epoxysuccinyl amides and the well-known function of related drugs. Intramolecular substituent effects are separated from intermolecular crystal packing effects on the electron density, which allows us to predict the conditions under which an experimental electron density investigation on trans-epoxysuccinyl amides will be possible. In this context, the special importance of the carboxylic acid function in the model compound for both crystal packing and biological activity is revealed through the novel tool of model energy analysis.
Original language | English |
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Article number | e3683 |
Pages (from-to) | 1-15 |
Number of pages | 15 |
Journal | Journal of Physical Organic Chemistry |
Volume | 30 |
Issue number | 11 |
Early online date | 24 Jan 2017 |
DOIs | |
Publication status | Published - 1 Nov 2017 |
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Dive into the research topics of 'Approaching an experimental electron density model of the biologically active trans-epoxysuccinyl amide group—Substituent effects vs. crystal packing'. Together they form a unique fingerprint.Projects
- 1 Finished
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Electrostatic Complementarity - A Unifying Principle in Molecular Crystal Structures
Spackman, M., Jayatilaka, D. & Grabowsky, S.
1/01/13 → 31/03/17
Project: Research