8B7C

Tubulin-maytansinoid-12 complex

Summary for 8B7C

• Entry DOI: 10.2210/pdb8b7c/pdb
• Descriptor: Tubulin alpha-1B chain, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, [(1~{S},2~{R},3~{S},5~{S},6~{S},16~{E},18~{E},20~{R},21~{S})-11-chloranyl-12,20-dimethoxy-2,5,9,16-tetramethyl-21-oxidanyl-8,23-bis(oxidanylidene)-4,24-dioxa-9,22-diazatetracyclo[19.3.1.1^{10,14}.0^{3,5}]hexacosa-10(26),11,13,16,18-pentaen-6-yl] 4-[2-(2-azanylhydrazinyl)ethyl]benzoate, ... (13 entities in total)
• Functional Keywords: cell cycle, tubulin fold, cytoskeleton, microtubule
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 6
• Total formula weight: 265353.68

Authors

Boiarska, Z.,Perez-Pena, H.,Abel, A.-C.,Marzullo, P.,Alvarez-Bernad, B.,Bonato, F.,Santini, B.,Horvath, D.,Lucena-Agell, D.,Vasile, F.,Sironi, M.,Diaz, J.F.,Steinmetz, M.O.,Prota, A.E.,Pieraccini, S.,Passarella, D. (deposition date: 2022-09-29, release date: 2023-08-23)

Primary citation

Boiarska, Z.,Perez-Pena, H.,Abel, A.C.,Marzullo, P.,Alvarez-Bernad, B.,Bonato, F.,Santini, B.,Horvath, D.,Lucena-Agell, D.,Vasile, F.,Sironi, M.,Diaz, J.F.,Prota, A.E.,Pieraccini, S.,Passarella, D.
Maytansinol Functionalization: Towards Useful Probes for Studying Microtubule Dynamics.
Chemistry, 29:e202203431-e202203431, 2023

PubMed Abstract: Maytansinoids are a successful class of natural and semisynthetic tubulin binders, known for their potent cytotoxic activity. Their wider application as cytotoxins and chemical probes to study tubulin dynamics has been held back by the complexity of natural product chemistry. Here we report the synthesis of long-chain derivatives and maytansinoid conjugates. We confirmed that bulky substituents do not impact their high activity or the scaffold's binding mode. These encouraging results open new avenues for the design of new maytansine-based probes.

PubMed: 36468686
DOI: 10.1002/chem.202203431

Experimental method

X-RAY DIFFRACTION (1.9 Å)