Slowly on, Slowly off: Bisubstrate-Analogue Conjugates of 5-Iodotubercidin and Histone H3 Peptide Targeting Protein Kinase Haspin was written by Kestav, Katrin;Viht, Kaido;Konovalov, Anton;Enkvist, Erki;Uri, Asko;Lavogina, Darja. And the article was included in ChemBioChem in 2017.Electric Literature of C11H13IN4O4 The following contents are mentioned in the article:
The atypical protein kinase haspin is a key player in mitosis by catalyzing the phosphorylation of Thr3 in histone H3, and thus ensuring the normal function of the chromosomal passenger complex. Here, we report the development of bisubstrate-analog inhibitors targeting haspin. The compounds were constructed by linking 5-iodotubercidin to the N terminus of histone H3 peptide. The new conjugates show high affinity (sub-nanomolar KD) towards haspin as well as slow kinetics of association and dissociation (residence time of several hours). This reflects a unique binding mode and translated into improved selectivity. The latter was confirmed in a biochem. binding/displacement assay with a panel of ten protein kinases, in a thermal shift assay with off-targets of 5-iodotubercidin (adenosine kinase and the Cdc2-like kinase family) and in assay with spiked HeLa cell lysate. This study involved multiple reactions and reactants, such as (2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4Electric Literature of C11H13IN4O4).
(2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4) belongs to tetrahydrofuran derivatives.Tetrahydrofuran has many industry uses as a solvent including in natural and synthetic resins, high polymers, fat oils, rubber, polymer. It is more basic than diethyl ether and forms stronger complexes with Li+, Mg2+, and boranes. It is a popular solvent for hydroboration reactions and for organometallic compounds such as organolithium and Grignard reagents.Electric Literature of C11H13IN4O4
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem