Predicting hydration propensities of biologically relevant α-ketoamides

Henry B. Wedler, Teresa A. Palazzo, Ryan P. Pemberton, Christian S. Hamann, Mark J. Kurth, Dean J. Tantillo

Research output: Contribution to journalArticle

Abstract

Quantum chemical calculations coupled to experiments were used to predict covalent hydration propensities of biologically relevant α-ketoamides. Experimentally determined hydration equilibrium constants for related ketones and aldehydes were compared to computationally determined values to develop a method for predicting hydration equilibrium constants. This method was used on six newly synthesized α-ketoamides to experimentally verify computational predictions. A correlation between calculation and experiment was observed and applied to models of several pertinent APIs. Our results indicate that the keto form is favored for practically all α-ketoamides in biological environs.

Original languageEnglish (US)
Pages (from-to)4153-4157
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number19
DOIs
StatePublished - Oct 1 2015

Fingerprint

Hydration
Equilibrium constants
Ketones
Aldehydes
Application programming interfaces (API)
Experiments
Environ

Keywords

  • Density functional theory
  • Hydration propensity
  • Predictive methods
  • Theory versus experiment
  • α-Ketoamide

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Wedler, H. B., Palazzo, T. A., Pemberton, R. P., Hamann, C. S., Kurth, M. J., & Tantillo, D. J. (2015). Predicting hydration propensities of biologically relevant α-ketoamides. Bioorganic and Medicinal Chemistry Letters, 25(19), 4153-4157. https://doi.org/10.1016/j.bmcl.2015.08.010

Predicting hydration propensities of biologically relevant α-ketoamides. / Wedler, Henry B.; Palazzo, Teresa A.; Pemberton, Ryan P.; Hamann, Christian S.; Kurth, Mark J.; Tantillo, Dean J.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 25, No. 19, 01.10.2015, p. 4153-4157.

Research output: Contribution to journalArticle

Wedler, HB, Palazzo, TA, Pemberton, RP, Hamann, CS, Kurth, MJ & Tantillo, DJ 2015, 'Predicting hydration propensities of biologically relevant α-ketoamides', Bioorganic and Medicinal Chemistry Letters, vol. 25, no. 19, pp. 4153-4157. https://doi.org/10.1016/j.bmcl.2015.08.010
Wedler HB, Palazzo TA, Pemberton RP, Hamann CS, Kurth MJ, Tantillo DJ. Predicting hydration propensities of biologically relevant α-ketoamides. Bioorganic and Medicinal Chemistry Letters. 2015 Oct 1;25(19):4153-4157. https://doi.org/10.1016/j.bmcl.2015.08.010
Wedler, Henry B. ; Palazzo, Teresa A. ; Pemberton, Ryan P. ; Hamann, Christian S. ; Kurth, Mark J. ; Tantillo, Dean J. / Predicting hydration propensities of biologically relevant α-ketoamides. In: Bioorganic and Medicinal Chemistry Letters. 2015 ; Vol. 25, No. 19. pp. 4153-4157.
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