Energy basis of recognition of base pair for platinum-based antitumour drug ZD0473 and cisplatin |
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Authors: | Lan Hao XiChen Li HongWei Tan GuangJu Chen and MuXin Jia |
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Institution: | (1) College of Chemistry, Beijing Normal University, Beijing, 100875, China;(2) Beijing General Research Institute of Mining and Metallurgy, Beijing, 100044, China |
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Abstract: | Platinum-based antitumour drug ZD0473 was designed to reduce the cisplatin resistance to the tumor cells. In this paper, the
mixed method of molecular mechanics and quantum chemistry, HF/lanl2dz// MM/uff and B3LYP/lanl2dz//6-31G*, are used to investigate
the differences between four types of GG, 3′AG5′, 3′GA5′, and AA complexes, which are formed from four discrete DNA fragments
recognized by ZD0473 and cisplatin. The results show that the binding interaction of both ZD0473 and cisplatin drugs with
the GG base pair is much stronger than with other base pairs, namely the recognition capability of such drugs to the GG base
pair is more considerable. Moreover, the interaction of four complexes of ZD0473 with DNA fragments is stronger than that
of cisplatin with corresponding DNA fragments, which indicates the stronger binding capability of ZD0473 with DNA fragments
and high antitumour activity of ZD0473. The main reason for easier forming of 3′GA5′ complex than the 3′AG5′ one is that the
drug molecule prefers to bind with a single G base to form a monoligand compound firstly; then the configuration transformation
from such monoligand compound to the bi-ligand one is limited.
Supported by the National Natural Science Foundation of China (Grant Nos. 20673011, 20231010, 20631020) and the Major State
Basic Research Development Programs (Grant No. G2004CB719900) |
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Keywords: | ZD0473 MM/uff//HF/lanl2dz DNA fragment GG 3′ AG5′ 3′ GA5′ |
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