A simple protocol to estimate differences in protein binding affinity for enantiomers without prior resolution of racemates

Angewandte Chemie - International Edition

Volumn 45, Issue 6, 2006, Pages 985-989

  Fokkens, Jasmine ^a   Klebe, Gerhard ^a  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

Author keywords

Calorimetry; Drug design; Enantioselectivity; Ligand effects; Protein structures

Indexed keywords

DRUG DESIGN; ENANTIOSELECTIVITY; LIGAND EFFECTS; PROTEIN STRUCTURES;

CALORIMETRY; ISOTHERMS; PROTEINS; TITRATION;

BINDING ENERGY;

PROTEIN; SERINE PROTEINASE INHIBITOR; THROMBIN; TRYPSIN;

ARTICLE; CALORIMETRY; CHEMISTRY; METABOLISM; PROTEIN BINDING; STEREOISOMERISM; X RAY CRYSTALLOGRAPHY;

CALORIMETRY; CRYSTALLOGRAPHY, X-RAY; PROTEIN BINDING; PROTEINS; SERINE PROTEINASE INHIBITORS; STEREOISOMERISM; THROMBIN; TRYPSIN;

EID: 32044460444     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200502302     Document Type: Article

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18. d values of ca. 50-200 reveals well-resolved two-step titration curves. However, the intensity of a recorded ITC signal is determined by the absorbed or released heat, which correlates with the enthalpic contribution to the binding process. Only if the free energy of binding of both enantiomers factorizes similarly into enthalpic and entropic contributions such a straightforward correlation with the binding-constant difference will be possible. However, such similar behavior of both enantiomers is not necessarily the case.
19. The crystal structures discussed herein are available from the Protein Data Bank (PDB) under the codes 1Y3U, 1Y3V, 1Y3W, 1Y3X, and 1Y3Y.