Item type:Thesis, Open Access

The well-tempered Thrombin - A systematic crystallographic and calorimetric study on the thermodynamics of serine-protease inhibition

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Date

2009-11-24

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Philipps-Universität Marburg
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Abstract

The presented study contributes to the fundamental understanding of molecular recognition of small molecules by a macromolecular host protein. The biophysical properties of a large set of systematically varied thrombin inhibitors were anatomized in detail. In particular the combination of structural information from X-ray crystallography with thermodynamic data from microcalorimetry allowed following the thermodynamically relevant differences resulting in the binding process. The approach of systematically varying biophysical properties of protein inhibitors in small steps permits conclusive statements on the contribution of individual functionalities to binding affinity, as the outstanding complexity of the binding thermodynamics could be reduced to the comparison of closely related inhibitors. Reorganization of solute molecules was explicitly considered in all discussions of the factors determining the widely varying binding affinity of the inhibitors to their target.

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Dates
Created: 2009Issued: 2009-11-24Updated: 2011-08-10
DOI
https://doi.org/10.17192/z2009.0698
Faculty
Fachbereich Pharmazie
Publisher
Philipps-Universität Marburg
Language
eng
Data types
DoctoralThesis
Keywords
MikrokalorimetrieKristallographieStructure based drug-designWirkstoffdesignThermodynamik
DFG-subjects
ThrombinArzneimitteldesign
DDC-Numbers
500
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2009.0698
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Baum, Bernhard (139534571): The well-tempered Thrombin - A systematic crystallographic and calorimetric study on the thermodynamics of serine-protease inhibition. : Philipps-Universität Marburg 2009-11-24. DOI: https://doi.org/10.17192/z2009.0698.

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