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Understanding the impact of anticancer halogenated inhibitors and various functional groups (X = Cl, F, CF3, CH3, NH2, OH, H) of casein kinase 2 (CK2)
Journal of Biomolecular Structure and Dynamics ( IF 4.4 ) Pub Date : 2020-12-29 , DOI: 10.1080/07391102.2020.1866075
Palanisamy Deepa 1 , Duraisamy Thirumeignanam 2
Affiliation  

Abstract

Main focus of study is to understand potency of halogen (X = Br) atom that exists in tetrabromobenzotriazole (TBB) derivatives of crystal CK2 ligand along with hinge region amino acids (VAL45, PHE113, GLU114, VAL116, ASN118) through interaction energy analysis. In turn to attain profound insight on nature of stabilization of core CK2 ligands: 1ZOE-L1, 1ZOG-L2, 1ZOH-L3, 2OXX-L4, 2OXY-L5, 3KXG-L6, 3KXH-L7 -L7 and 3KXM-L8, having four bromine atoms, we attempted to mutate all bromine (X = Br) atoms by various functional groups (X = Cl, F, CF3, CH3, NH2, OH, H) and binding strength along with amino acids was calculated. Most stable ligands exist in mutated NH2 functional groups: 1ZOG-L2, 1ZOH-L3, 2OXX-L4, 3KXM-L8 having interaction energy as −5.21, −14.87, −6.69 and −11.72 kcal/mol respectively, revealing strong binding strength. Second most stable mutated Cl functional group ligands also play a major role in 1ZOH-L3, 2OXX-L4 and 3KXM-L8 having interaction energy as −6.89, −5.37, and −10.48 kcal/mol respectively. Overall, this study will pave way for crystal growth and medicinal chemist to have cleared perceptive about structural properties of CK2 halogenated ligands with new insight on CK2 mutated functional group ligands. Further, it insists us to reuse existing CK2 crystal ligand with more preferable suggested binding contacts in course of new functional groups that lead to anticancer affinity.

Communicated by Ramaswamy H. Sarma



中文翻译:

了解抗癌卤化抑制剂和酪蛋白激酶 2 (CK2) 的各种官能团(X = Cl、F、CF3、CH3、NH2、OH、H)的影响

摘要

研究的主要重点是通过相互作用能分析了解晶体CK2配体的四溴苯并三唑(TBB)衍生物中存在的卤素(X = Br)原子以及铰链区氨基酸(VAL45,PHE113,GLU114,VAL116,ASN118)的效力。反过来深入了解核心 CK2 配体的稳定性:1ZOE-L1、1ZOG-L2、1ZOH-L3、2OXX-L4、2OXY-L5、3KXG-L6、3KXH-L7 -L7 和 3KXM-L8,具有四个溴原子,我们试图通过各种官能团(X = Cl、F、CF 3、CH 3、NH 2、OH、H)突变所有溴(X = Br)原子,并计算结合强度和氨基酸。最稳定的配体存在于突变的 NH 2中官能团:1ZOG-L2、1ZOH-L3、2OXX-L4、3KXM-L8,相互作用能分别为-5.21、-14.87、-6.69和-11.72 kcal/mol,显示出很强的结合强度。第二个最稳定的突变 Cl 官能团配体也在 1ZOH-L3、2OXX-L4 和 3KXM-L8 中起主要作用,其相互作用能分别为 -6.89、-5.37 和 -10.48 kcal/mol。总体而言,这项研究将为晶体生长和药物化学家铺平道路,使他们对 CK2 卤化配体的结构特性有了清晰的认识,并对 CK2 突变的官能团配体有了新的认识。此外,它坚持我们在导致抗癌亲和力的新官能团的过程中重复使用现有的 CK2 晶体配体与更优选的建议结合接触。

由 Ramaswamy H. Sarma 传达

更新日期:2020-12-29
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