Stoichiometric and substoichiometric inhibition of tubulin self-assembly by colchicine analogues

Biochemistry
B Perez-RamirezS N Timasheff

Abstract

The mechanism of the stoichiometric and substoichiometric inhibitions of tubulin self-assembly by several structural analogues of colchicine (COL) was investigated. The inhibition data were analyzed in terms of a simple model that takes into consideration Kg, the normal microtubule growth constant, equal to Cr-1 (Cr is the critical concentration for microtubule formation), and Kb, the binding constant of the drug to tubulin. In this manner, the value of the microtubule inhibition constant (Ki), which is the binding constant of the tubulin-drug complex to the end of a growing microtubule (which stops the microtubule growth), was determined. The results of the analysis of microtubule inhibition by the various colchicine analogues show that all the inhibitions can be expressed reasonably by this model. The strongest inhibitors found were colchicine (COL), allocolchicine (ALLO), and the biphenyl keto analogue 2,3,4-trimethoxy-4'-acetyl-1,1'-biphenyl (TKB), which had essentially identical values of Ki = (2.1 +/- 0.3) x 10(6) M(-1). MTC, the two-ring analogue of colchicine, was weaker (Ki = 5.6 x 10(5) M(-1). A most striking result was that tropolone methyl ether (TME), which is ring C of COL, and which binds very weakly to tubulin (...Continue Reading

References

Nov 15, 1974·Journal of Molecular Biology·B J Berne
Nov 15, 1974·Journal of Molecular Biology·F GaskinM L Shelanski
Aug 1, 1980·European Journal of Biochemistry·A Lambier, Y Engelborghs

❮ Previous
Next ❯

Citations

Apr 9, 2002·Bioorganic & Medicinal Chemistry·Mark E Janik, Susan L Bane
Oct 22, 2011·Advanced Drug Delivery Reviews·Jan JezekBernardo Perez-Ramirez
Dec 31, 2005·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Pankaj Kumar MishraDebashish Chowdhury
Jul 14, 2020·Journal of Medicinal Chemistry·María A OlivaJ Fernando Díaz
Sep 3, 2021·Biophysics Reviews·Kirk AuneMarina Timasheff Charles

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Archives of Biochemistry and Biophysics
J D Sakura, S N Timasheff
Archives of Biochemistry and Biophysics
L Weil, S N Timasheff
Archives of Biochemistry and Biophysics
S N TimasheffJ G KIRKWOOD
© 2021 Meta ULC. All rights reserved