Interactions of 5- iodotubercidin with binding site of serine/threonine – protein kinase Haspin; an ONIOM approach study was written by Hadad, Babak Khjalili;Sadeh, Hadis Soltani;Arman, Foroozan;Esmaeilzadeh, Fatemeh. And the article was included in Recent Advances in Electrical Engineering Series in 2012.Synthetic Route of C11H13IN4O4 The following contents are mentioned in the article:
Each daughter cell has to receive the correct complement of chromosomes in mitosis. Some of mitotic kinases are critical to manage individualization of chromosomes. Haspin is newly discovered kinase with regulatory effect. Haspin protein has serine/ threonine kinase activity. Thr 3 of Histone H3 is the only substrate of Haspin to do phosphorylation. Highly potent and selective ligands are developed using organo non-metallic inhibitors. Non- metal centers prepare a big chem. chamber. Uncontrolled growth, survival and metastasis are some characteristics of cancer. These are caused because of perturbation of regulatory signaling pathways specially, kinases. Chems. specifically inhibits such regulators, are targets for chemotherapy. Haspin (PDB ID: 3IQ7) is analyzed in present research. H-bond and Hydrophobic pocket interactions are studied with both docking and ONIOM methods. 5- Iodotubercidin-the mimetic structure of ATP- is one of effective inhibitors. To increase the efficacy and its attraction to binding site of the Haspin, it is suggested to modify the structure of drug to increase H-bond attraction. The main engaged amino acids in binding site that are responsible to produce H- bonds, are Glu606, Gly608, Asp611 and Gly653. By modifying the drug it is possible to increase some sites, to engage more amino acids, close to present pocket. Gln614, Arg616 are closest functional amino acids based on primary structure. The same process will be done for hydrophobic pocket where Ile490, Gly491, Val498, Ala509, Phe609, Leu656, and He686 are the main amino acids. Phe495, Phe499, He685, Val508 and Phe605 are suggested to be the next targets. Oxygen and fluorine are found more effective than iodine to make the system more stable. It is suggested to use the oxygen or fluorine as two electroneg. elements instead of the iodine. 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: 24386-93-4Synthetic Route 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 (THF), or oxolane, is mainly used as a precursor to polymers. Being polar and having a wide liquid range, THF is a versatile solvent. Oxidations have also proved to be valuable and efficient approaches to chiral tetrahydrofuran derivatives.Synthetic Route of C11H13IN4O4
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem