Entropy and Enthalpy in the Activity of Tubulin-Based Antimitotic Agents
Microtubules are important biological targets of antitumor chemotherapy. Tubulin polymerization inhibitors (TPIs) hinder polymerization whereas microtubule stabilizing agents (MSAs) promote tubulin polymerization and stabilize microtubules. The goal of enhancing binding affinity through
favorable (positive) entropic contributions, a significant part of medicinal chemistry dogma, hinges on a rather simplistic assumption that ligand-protein binding interactions are primarily entropically driven. In turn, individual contributions of enthalpy and entropy to the overall potency
of small molecules rarely are determined. Herein, we describe various antimitotic agents whose interactions with tubulin were explored and in which the individual enthalpic and entropic contributions were evaluated. These examples clearly demonstrate that the binding affinities of small molecules
with their target proteins are more complex than often articulated; one should exercise caution when rationalizing the relative activity of these molecules and their analogues.
Keywords: Microtubules; antimitotic agents; binding afftinity; enthalpy; entropy; tubulin
Document Type: Research Article
Publication date: 01 January 2009
- Current Chemical Biology aims to publish full-length and mini reviews on exciting new developments at the chemistry-biology interface, covering topics relating to Chemical Synthesis, Science at Chemistry-Biology Interface and Chemical Mechanisms of Biological Systems.
Current Chemical Biology covers the following areas: Chemical Synthesis (Syntheses of biologically important macromolecules including proteins, polypeptides, oligonucleotides, oligosaccharides etc.; Asymmetric synthesis; Combinatorial synthesis; Diversity-oriented synthesis; Template-directed synthesis; Biomimetic synthesis; Solid phase biomolecular synthesis; Synthesis of small biomolecules: amino acids, peptides, lipids, carbohydrates and nucleosides; and Natural product synthesis).
Science at Chemistry-Biology Interface (Chemical informatics; Macromolecular catalysts and receptors; Enzymatic synthesis; Biosynthetic engineering; Combinatorial biosynthesis; Plant cell based chemistry; Bacterial and viral cell based chemistry; Chemistry of cellular processes in plants/animals; Receptor chemistry; Cell signaling chemistry; Drug design through understanding of disease processes; Synthetic biology; New high throughput screening techniques; Small molecular array fabrication; Chemical genomics; Chemical and biological approaches to carbohydrates proteins and nucleic acids design; Chemical and biological regulation of biosynthetic pathways; and Unnatural biomolecular analogs). - Editorial Board
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