The thermodynamics of vinca alkaloid-induced tubulin spirals formation.

The thermodynamics of vinca alkaloid-induced tubulin spirals formation. Research Abstract Details 

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The thermodynamics of vinca alkaloid-induced tubulin spirals formation. Abstract Text:

Sharon Lobert,Jeffrey W Ingram,John J Correia,

Vinca alkaloids are antimitotic, anticancer agents that induce tubulin to form spiral polymers at physiological protein concentrations. We used sedimentation velocity to investigate the effects of six vinca alkaloids on tubulin spiraling. Fitting to a Wyman linkage model reveals a drug dependent change of over two orders of magnitude in spiraling potential, K(1)K(2). Thermodynamic analysis of LnK(1)K(2) data demonstrates large and positive DeltaS values, indicating that tubulin spiral formation is entropically-driven. From the curvature in van't Hoff plots of vinblastine data, we estimate DeltaC(p) for GTP and GDP conditions to be -439 and -396 cal/mol K. Partitioning of DeltaS into the hydrophobic effect, DeltaS(HE), change in rotational/translational freedom, DeltaS(RT) and change in protein conformation, DeltaS(other), demonstrates that the major driving force for tubulin spiral formation is burial of hydrophobic surfaces and that protein conformational changes do not make a significant contribution. Spiraling potential is an indicator of antimitotic activity in vivo, although turbidity studies indicate that there is no correlation between spiraling potential and microtubule inhibition in vitro. Mechanisms that explain this discrepancy are discussed.

The thermodynamics of vinca alkaloid-induced tubulin spirals formation. Publishing Authors By Initials

S Lobert,JW Ingram,JJ Correia,

For similar heterocyclic compounds: alkaloids: indole alkaloids: secologanin tryptamine alkaloids: vinca alkaloids research abstracts see: heterocyclic compounds: alkaloids: indole alkaloids: secologanin tryptamine alkaloids: vinca alkaloids research

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The thermodynamics of vinca alkaloid-induced tubulin spirals formation. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Biophysical chemistry

VOLUME: 126

Page Numbers: 50-8

Journal Abbreviation: Biophys. Chem.

ISSN: 0301-4622

DAY: 6

MONTH: 06

YEAR: 2006

The thermodynamics of vinca alkaloid-induced tubulin spirals formation. Information

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LANGUAGE: eng

NlmUniqueID: 403171

The thermodynamics of vinca alkaloid-induced tubulin spirals formation. Keywords Mesh Terms:

KEYWORDS: Vinca Alkaloids

MESH TERMS: toxicity

Chemical & Substance for Abstract: The thermodynamics of vinca alkaloid-induced tubulin spirals formation. Information

Substance Name: Vinca Alkaloids

Registry Number: 0

Grant and Affiliation Information for The thermodynamics of vinca alkaloid-induced tubulin spirals formation.

AFFILIATION: School of Nursing, University of Mississippi Medical Center, Jackson, MS 39216, USA.

Country: Netherlands

AGENCY: United States NINR

GRANT: NR04780

ACRONYM: NR

MEDLINETA: Biophys Chem

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