Zhao Lijiao

The Induction and Repair of DNA Interstrand Crosslinks and Implications in Cancer Chemotherapy

DNA interstrand crosslinks (ICLs) can be induced by numerous endogenous and exogenous chemical agents with the capacity of covalently binding to two base sites in the two strands of the DNA duplex. A series of normal DNA metabolism processes are affected by ICLs. For example, DNA replication and transcription are interfered during cell division, which is fatal to cell survival. In cancer cells, the induction of ICLs is a significant target for cancer chemotherapies. However, the formation of ICLs in cancer cells can be weakened by the repair mechanisms of DNA damage, which results in resistance to chemotherapies. Therefore, it is necessary to develop highly effective ICL agents for the purpose of achieving good chemotherapeutic effects. Furthermore, the combination of ICL agents with inhibitors of ICL repair is a promising strategy for the clinical treatment of cancer. This review summarizes the development of several types of ICL agents as chemotherapies over the past decades and the mechanisms underlying the repair of DNA ICLs. The potential of ICL repair inhibitors for combination therapy with ICL agents in cancer treatment is also discussed.

Research on the Quantitative Structure-Carcinogenic Activity Relationship of N-Nitroso Compounds

According to the results of quantitative pattern recognition for 153 N-nitroso compounds (NNCs) based on Di-region theory, it is put forward that the esters formed from the metabolism of NNCs on beta- or gamma-position could be alkylating agents of DNA bases with the anchimeric assistance of the N-nitroso group. This viewpoint, combined with the conception of alpha-metabolism activation, can explain the structure-carcinogenic activity relationship reasonably. Quantum chemistry ab initio calculations are carried out to study the activity of different metabolites of NNCs in direct alkylation and the anchimeric assistant processes. By ONIOM method, a QM/MM calculation is carried out to study the crosslink of DNA base pair by methylalkylnitrosamines. Based on the computational results, the quantitative structure and carcinogenic activity relationship of 58 N-nitrosoureas that have got animal carcinogenicity tests reported are studied

N-phosphorylamino acids and Penta-coordinate Phosphorous Compounds in the Chemical process of Life

N-phosphorylamino acids can react to form esters, peptides, phosphoryl ester-exchanged products and phosphoryl group migration products under mild conditions which are very important in researches on the origin of life. It has been proposed that the penta-coordinate phosphorous compounds might be the common intermediates of these reactions, which are the key factor to determine the activities. In this paper, the mechanisms of series reactions involving N-phosphorylaminoacids and penta-coordinate phosphorous compounds are studied with computational chemistry methods