Computational comparison of microtubule-stabilising agents laulimalide and peloruside with taxol and colchicine

Pineda, Oriol; Farràs, Jaume; Maccari, Laura; Manetti, Fabrizio; Botta, Maurizio; Vilarrasa, Jaume

doi:10.1016/j.bmcl.2004.07.053

Cited by 67 publications

(63 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Peloruside A and Laulimalide-A site in ␣-tubulin, which corresponds to the taxane binding pocket in ␤-tubulin, has been proposed as a possible binding site for PelA and LML based on computational docking experiments (23). Our deuterium incorporation data, however, suggested that this site in ␣-tubulin is an unlikely candidate for the binding of PelA and LML.…”

Section: Region-specific Alterations In Deuterium Incorporation (Hdx)mentioning

confidence: 64%

Hallmarks of Molecular Action of Microtubule Stabilizing Agents

Baine¹,

Menon²,

Yang³

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Section: Region-specific Alterations In Deuterium Incorporation (Hdx)mentioning

confidence: 64%

Hallmarks of Molecular Action of Microtubule Stabilizing Agents

Baine¹,

Menon²,

Yang³

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…Table 1. Structural and biological properties of taxanes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) and epothilones (15,16,(18)(19)(20)(21) used in this study location of paclitaxel binding site in the β subunit but lacked the resolution to exactly define the whole ligand conformation. As a consequence, not all the amino acid residues were well solved and paclitaxel was replaced by the X-ray structure of docetaxel.…”

Section: Resultsmentioning

confidence: 99%

“…13 The authors suggest that tubulin displays a promiscuous binding pocket and that ligands like paclitaxel and epothilone exploits the tubulin-binding pocket in an independent manner. Accordingly, computational studies about the binding and pharmacophores for epothilones but also other microtubule-stabilizing agents as laulimalide, peloruside and colchicines, 14 will be further revised.…”

mentioning

confidence: 99%

A pharmacophore modeling approach to design new taxol® mimics: towards the synthesis of potential anticancer and MDR-reversing agent

Renzulli¹,

Rocheblave²,

Avramova³

et al. 2006

Arkivoc

Self Cite

View full text Add to dashboard Cite

The remarkable therapeutic importance of taxane diterpenoids as anticancer drugs and their challenging structural complexity have stimulated worldwide enormous efforts. Our group developed a theoretic quantitative model describing the relationship between structure and biological activity of microtubules-stabilizing anticancer agents (MSAAs) aimed at gaining an insight into the specific structural features required for the ligand-receptor binding. The model was demonstrated to be able to estimate/predict the microtubule-stabilising activity for a series of taxanes and provided further details about the influence of each pharmacophore point on the ligand binding affinity. Molecular modeling studies from our group revealed that modified Taxuspines U and X could adopt a conformation similar to the bioactive conformation of paclitaxel and can be well accommodated within the pseudoreceptor model. Following the suggestions coming from the model we rationally designed and synthesized new simplified taxuspine U analogues. In particular, we developed a new methodology for the synthesis of such compounds involving a macrocyclisation reaction via RCM in presence of different functional groups.

show abstract

“…The binding site 2 is made up of b-tubulin residues Asp224, His227, Thr274, Arg276, Arg282 and Gly360, and it just located in the well-known taxane site. The binding site 3 is distinctly different from the site locating in B9-B10 loop extension of a-tubulin 11,12 , and it is a new site comprised of a-tubulin residues Ser158, Gly162, Ser198 and Pro263. In short, the taxane site, the alternative site and the new site 3 are possible to be the binding sites of PLA.…”

Section: Molecular Dockingmentioning

confidence: 93%

“…Previous experimental studies discovered that PLA did not compete with taxane site drugs for binding to microtubules 8 , instead, it could synergize with them 10 . The initial studies through molecular docking and TR-NOESY nuclear magnetic resonance (NMR) proposed that the binding site of PLA was on a-tubulin 11,12 . However, Huzil et al 13 proposed a specific PLA-binding site that was adjacent to the taxane-binding site in the b-tubulin by using hydrogen-deuterium exchange mass spectrometry (HDXMS).…”

Section: Introductionmentioning

confidence: 99%

Docking and molecular dynamics studies of the binding between Peloruside A and tubulin

Liao

Chen

et al. 2013

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

The molecular docking, MD simulation and binding free energy calculation were performed to explore the probable binding modes between PLA and tubulin. Through docking study, three possible binding sites for PLA were speculated as follows: the taxane site, the alternative site and a new site in a-tubulin. Then, 12.0 ns MD simulations show that these binding modes predicted by docking have been changed more or less, whereas the MD simulations offer more reliable binding details. The MM-PBSA binding free-energy calculations reasonably identify that the taxane site is the most favorable binding site of PLA and the alternative site is the secondary one, which can be used to explain some experimental facts. These studies theoretically resolve the priority of binding sites for PLA and offer the reliable binding modes between PLA and tubulin, and thus help to understanding the action mechanism for this kind of inhibitor.

show abstract

Computational comparison of microtubule-stabilising agents laulimalide and peloruside with taxol and colchicine

Cited by 67 publications

References 46 publications

Hallmarks of Molecular Action of Microtubule Stabilizing Agents

Hallmarks of Molecular Action of Microtubule Stabilizing Agents

A pharmacophore modeling approach to design new taxol® mimics: towards the synthesis of potential anticancer and MDR-reversing agent

Docking and molecular dynamics studies of the binding between Peloruside A and tubulin

Contact Info

Product

Resources

About