The author of 《Designing a chemical inhibitor for the AAA protein spastin using active site mutations》 were Cupido, Tommaso; Pisa, Rudolf; Kelley, Megan E.; Kapoor, Tarun M.. And the article was published in Nature Chemical Biology in 2019. Category: pyrimidines The author mentioned the following in the article:
Spastin is a microtubule-severing AAA (ATPases associated with diverse cellular activities) protein needed for cell division and intracellular vesicle transport. Currently, we lack chem. inhibitors to probe spastin function in such dynamic cellular processes. To design a chem. inhibitor of spastin, we tested selected heterocyclic scaffolds against wild-type protein and constructs with engineered mutations in the nucleotide-binding site that do not substantially disrupt ATPase activity. These data, along with computational docking, guided improvements in compound potency and selectivity and led to spastazoline, a pyrazolyl-pyrrolopyrimidine-based cell-permeable probe for spastin. These studies also identified spastazoline-resistance-conferring point mutations in spastin. Spastazoline, along with the matched inhibitor-sensitive and inhibitor-resistant cell lines we generated, were used in parallel experiments to dissect spastin-specific phenotypes in dividing cells. Together, our findings suggest how chem. probes for AAA proteins, along with inhibitor resistance-conferring mutations, can be designed and used to dissect dynamic cellular processes. In the experiment, the researchers used 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Category: pyrimidines)
2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Category: pyrimidines
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia