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

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
1. Verfasser: Baum, Bernhard
Beteiligte: Klebe, Gerhard (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Englisch
Veröffentlicht: Philipps-Universität Marburg 2009
Pharmazeutische Chemie
Schlagworte:
Online Zugang:PDF-Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
DOI:https://doi.org/10.17192/z2009.0698