Synthesis and Tubulin-Binding Properties of Some AC- and ABC-Ring Analogs of Allocolchicine

1992 ◽  
Vol 45 (12) ◽  
pp. 1967 ◽  
Author(s):  
MG Banwell ◽  
JM Cameron ◽  
M Corbett ◽  
JR Dupuche ◽  
E Hamel ◽  
...  
Keyword(s):  
Tubulin Polymerization ◽  
Binding Properties ◽  
Antimitotic Agent ◽  
Active Compounds ◽  
X Ray ◽  
Tubulin Binding

Fourteen analogues [compounds (8), (9) and (11)-(22)] of the powerful antimitotic agent allocolchicine (5) have been prepared and evaluated for their ability to prevent tubulin polymerization. The X-ray structure of one of the more active compounds, tricycle (20), is reported.

Synthesis, X-Ray Crystal Structure and Tubulin- Binding Properties of a Benzofuran Analogue of the Potent Cytotoxic Agent Combretastatin A4

1999 ◽  
Vol 52 (8) ◽  
pp. 767 ◽  
Author(s):  
Martin G. Banwell ◽  
Bernard L. Flynn ◽  
Ernest Hamel ◽  
Anthony C. Willis
Keyword(s):  
Crystal Structure ◽  
Cytotoxic Agent ◽  
Binding Agent ◽  
Binding Properties ◽  
Antimitotic Agent ◽  
X Ray ◽  
Combretastatin A4 ◽  
Tubulin Binding

The benzofuran (4), a ring-fused analogue of the potent antimitotic agent combretastatin A4 (1), has been prepared by a convergent route involving 5-endo-dig iodocyclization of o-hydroxytolan (5) as the key step. Compound (4), which has been characterized crystallographically as well as spectroscopically, is inactive as a tubulin-binding agent.

scholarly journals Structural Basis of Tubulin Recruitment and Assembly by Tumor Overexpressed Gene (TOG) domain array Microtubule Polymerases

2018 ◽  
Author(s):  
Stanley Nithianantham ◽  
Brian D Cook ◽  
Fred Chang ◽  
Jawdat Al-Bassam
Keyword(s):  
Exchange Rates ◽  
Underlying Mechanism ◽  
Structural Basis ◽  
Tubulin Polymerization ◽  
X Ray ◽  
Tubulin Binding ◽  
Overexpressed Gene

AbstractXMAP215/Stu2/Alp14 proteins accelerate microtubule plus-end polymerization by recruiting tubulins via arrays of Tumor Overexpressed Gene (TOG) domains. The underlying mechanism of these arrays as microtubule polymerases remains unknown. Here, we describe the biochemical and structural basis for TOG domain arrays in recruiting and polymerizing tubulins. Alp14 binds four tubulins via dimeric TOG1-TOG2 arrays, each with distinct exchange rates. X-ray structures reveal pseudo-dimeric square-shaped assemblies in which four TOG domains position four unpolymerized tubulins in a polarized wheel-like configuration. Crosslinking confirms square assemblies form in solution, and inactivation of their interfaces destabilizes square organizations without influencing tubulin binding. Using an approach to modulate tubulin polymerization, we determined a X-ray structure showing an unfurled assembly in which TOG1 and TOG2 uniquely bind two polymerized tubulins. Our findings suggest a new microtubule polymerase model in which TOG arrays recruit tubulins by forming square assemblies, which then unfurl facilitating their concerted polymerization into protofilaments.

scholarly journals Structural basis of tubulin recruitment and assembly by microtubule polymerases with tumor overexpressed gene (TOG) domain arrays

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Stanley Nithianantham ◽  
Brian D Cook ◽  
Madeleine Beans ◽  
Fei Guo ◽  
Fred Chang ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Exchange Rate ◽  
Structural Basis ◽  
Tubulin Polymerization ◽  
X Ray ◽  
Tubulin Binding ◽  
Overexpressed Gene

XMAP215/Stu2/Alp14 proteins accelerate microtubule plus-end polymerization by recruiting tubulins via arrays of tumor overexpressed gene (TOG) domains, yet their mechanism remains unknown. Here, we describe the biochemical and structural basis for TOG arrays in recruiting and polymerizing tubulins. Alp14 binds four tubulins via dimeric TOG1-TOG2 subunits, in which each domain exhibits a distinct exchange rate for tubulin. X-ray structures revealed square-shaped assemblies composed of pseudo-dimeric TOG1-TOG2 subunits assembled head-to-tail, positioning four unpolymerized tubulins in a polarized wheel-like configuration. Crosslinking and electron microscopy show Alp14-tubulin forms square assemblies in solution, and inactivating their interfaces destabilize this organization without influencing tubulin binding. An X-ray structure determined using approach to modulate tubulin polymerization revealed an unfurled assembly, in which TOG1-TOG2 uniquely bind to two polymerized tubulins. Our findings suggest a new microtubule polymerase model in which TOG arrays recruit tubulins by forming square assemblies that then unfurl, facilitating their concerted polymerization into protofilaments.

Semisyntheses, X-Ray Crystal Structures and Tubulin-Binding Properties of 7-Oxodeacetamidocolchicine and 7-Oxodeacetamidoisocolchicine

1992 ◽  
Vol 45 (10) ◽  
pp. 1577 ◽  
Author(s):  
MG Banwell ◽  
SC Peters ◽  
RJ Greenwood ◽  
MF Mackay ◽  
E Hamel ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Binding Properties ◽  
X Ray ◽  
Tubulin Binding

Commercially available (–)-colchicine (1) has been converted, via deacetylcolchiceine (4), into a mixture of 7-oxodeacetamidocolchicine (2) and 7-oxodeacetamidoisocolchicine (3). The X-ray structures and tubulin-binding properties of these title ketones are described.

scholarly journals X-ray structure of a molecular basket. Origin of its poor binding properties

1993 ◽  
Vol 112 (6) ◽  
pp. 400-403 ◽  
Author(s):  
C. F. Martens ◽  
R. P. Sijbesma ◽  
R. J. M. Klein Gebbink ◽  
R. J. M. Nolte ◽  
A. L. Spek
Keyword(s):  
Binding Properties ◽  
X Ray

Antitumor Agents. 192. Antitubulin Effect and Cytotoxicity of C(7)-Oxygenated Allocolchicinoids

1999 ◽  
Vol 64 (2) ◽  
pp. 217-228 ◽  
Author(s):  
Jian Guan ◽  
Xiao-Kang Zhu ◽  
Arnold Brossi ◽  
Yoko Tachibana ◽  
Kenneth F. Bastow ◽  
...  
Keyword(s):  
Cell Lines ◽  
Antitumor Agents ◽  
Human Tumor ◽  
Crystallographic Analysis ◽  
Antitumor Activities ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
X Ray ◽  
Tubulin Binding ◽  
Marked Resistance

Two allocolchicinoids 6 and 8, prepared from colchicine, together with allo compounds 9-11, made from 6 by reduction and regiodemethylation, were evaluated for antitubulin and antitumor activities. Structures of 6, 8, and 10 were confirmed by X-ray crystallographic analysis. Compounds 6, 8, and 9 have high tubulin binding affinity and display potent inhibitory activities against tubulin polymerization and solid human tumor cell lines. Particularly, drug-resistant KB cell lines, including KB-7d, KB-VCR, and KB-CPT, do not show marked resistance to these compounds.

2,3-Ethylene-bridged dihomooxacalix[4]arenes: synthesis, X-ray crystal structures and highly selective binding properties with anions

2018 ◽  
Vol 42 (13) ◽  
pp. 10689-10696 ◽  
Author(s):  
Lin An ◽  
Jia-wei Wang ◽  
Chan Wang ◽  
Shan-shan Zhou ◽  
Jing Sun ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Binding Properties ◽  
Selective Binding ◽  
X Ray

Three novel 2,3-ethylene-bridged p-tert-butyldihomooxacalix[4]arenes 3a–3c were selectively synthesized by direct O-alkylation of p-tert-butyldihomooxacalix[4]arene 1 with excess of 1,2-dibromoethane in controlled basic systems.

scholarly journals Dihomooxacalix[4]arene-Based Fluorescent Receptors for Anion and Organic Ion Pair Recognition

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4708
Author(s):  
Alexandre S. Miranda ◽  
Paula M. Marcos ◽  
José R. Ascenso ◽  
Mário N. Berberan-Santos ◽  
Rachel Schurhammer ◽  
...  
Keyword(s):  
Chiral Recognition ◽  
Aminobutyric Acid ◽  
Quantum Mechanical ◽  
Anion Receptor ◽  
Binding Properties ◽  
Cone Conformation ◽  
X Ray ◽  
Biologically Relevant ◽  
Alkylammonium Salts ◽  
Fluorescence Titrations

Fluorescent dihomooxacalix[4]arene-based receptors 5a–5c, bearing two naphthyl(thio)ureido groups at the lower rim via a butyl spacer, were synthesised and obtained in the cone conformation in solution. The X-ray crystal structures of 1,3- (5a) and 3,4-dinaphthylurea (5b) derivatives are reported. Their binding properties towards several anions of different geometries were assessed by 1H-NMR, UV-Vis absorption and fluorescence titrations. Structural and energetic insights of the naphthylurea 5a and 5b complexes were also obtained using quantum mechanical calculations. The data showed that all receptors follow the same trend, the association constants increase with the anion basicity, and the strongest complexes were obtained with F−, followed by the oxoanions AcO− and BzO−. Proximal urea 5b is a better anion receptor compared to distal urea 5a, and both are more efficient than thiourea 5c. Compounds 5a and 5b were also investigated as heteroditopic receptors for biologically relevant alkylammonium salts, such as the neurotransmitter γ-aminobutyric acid (GABA·HCl) and the betaine deoxycarnitine·HCl. Chiral recognition towards the guest sec-butylamine·HCl was also tested, and a 5:2 selectivity for (R)-sec-BuNH3+·Cl− towards (P) or (M) enantiomers of the inherently chiral receptor 5a was shown. Based on DFT calculations, the complex [(S)-sec-BuNH3+·Cl−/(M)-5a] was indicated as the more stable.

scholarly journals Synthesis, X-ray Structure, and Anion-Binding Properties of a Cryptand-Like Hybrid Calixpyrrole

2010 ◽  
Vol 75 (18) ◽  
pp. 6263-6266 ◽  
Author(s):  
Grazia Cafeo ◽  
Howard M. Colquhoun ◽  
Angela Cuzzola ◽  
Mario Gattuso ◽  
Franz H. Kohnke ◽  
...  
Keyword(s):  
Anion Binding ◽  
Binding Properties ◽  
X Ray
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