A novel N-methyl-D-aspartate receptor open channel blocker with in vivo neuroprotectant activity
Excitotoxicity has been implicated in the etiology of ischemic stroke, chronic neurodegenerative disorders, and very recently, in glioma growth. Thus, the development of novel neuroprotectant molecules that reduce excitotoxic brain damage is vigorously pu
Planells-Cases, Rosa,Montoliu, Carmina,Humet, Marc,Fernandez, Asia M.,Garcia-Martinez, Carolina,Valera, Elvira,Merino, Jaime M,Perez-Paya, Enrique,Messeguer, Angel,Felipo, Vicente,Ferrer-Montiel, Antonio
Positional Scanning Synthesis of a Peptoid Library Yields New Inducers of Apoptosis that Target Karyopherins and Tubulin
We describe the synthesis of a library of 11 638 N-alkylglycine peptoid trimers in a positional scanning format with adjustment of reaction conditions to account for different reactivities of the monomer building blocks. Evaluation of the library by high-content phenotypic screening for modulators of the cytoskeleton and mitosis resulted in the identification of two apoptosis-inducing peptoids, which, despite their structural similarity, target different proteins and cellular mechanisms. Whereas one peptoid binds to karyopherins, which mediate nuclear transport, the other N-alkylglycine trimer binds tubulin at the vinca alkaloid binding site.
Vendrell-Navarro, Glòria,Rúa, Federico,Bujons, Jordi,Brockmeyer, Andreas,Janning, Petra,Ziegler, Slava,Messeguer, Angel,Waldmann, Herbert