Recently, Associate Prof. Wang Tao of SUSTech Department of Biology cooperated with Prof. Yang Feng and Prof. Zhang Wei from School of Pharmacy, Nantong University, and published a paper on the most prestigious journal in medicinal chemistry－Journal of Medicinal Chemistry titled Developing Anticancer Ferric Prodrugs Based on the N-Donor Residues of Human Serum Albumin Carrier IIA Subdomain. The paper reported the latest progress in developing anticancer ferric prodrugs based on the N-donor residues of human serum albumin carrier for the first time.

Human Serum Albumin (HSA) is the most abundant protein in human blood plasma, whose concentrations in plasma can reach 5g/100mL. In the past decades, the physiological and pharmacological characteristics of HSA have been widely researched. As the most important carrier system, HSA can transport solutes in plasma to corresponding organs.

HSA is a kind of protein consisting of 585 amino acid residues, and has a molecular mass of 66.5 kDa. It has 35 cysteine residues, 34 of which form 17 pairs of disulfide bonds, making its structure very stable, with a half-life period of as long as 19 days. In its molecular structure, there are multiple areas capable of specifically binding small molecular drugs. It is the existence of multiple areas of drug binding that makes it possible for HSA to bind 70% of small molecular drugs. Therefore, it is a very popular field of study to take HSA as the drug carrier to prolong the half-life period of drugs within the body and reduce the toxicity of drugs at the same time. The most successful case is Abraxane®, the compound of the anticancer drug Paclitaxel based on HSA carrier developed by the Abraxis Bioscience. This drug greatly reduces the toxicity of Paclitaxel and noticeably increases its anti-tumor ability.

In the paper, researchers designed a series of anticancer ferric prodrugs by taking the IIA subdomain of HSA as carrier binding sites. By using the X-ray crystallography， they confirmed that components were bound on the binding sites of the HSA IIA domain as predicted. Through vivo experiments, they confirmed that the developed HSA anticancer ferric complex compound was more effective in treating tumors than monomeric compound, which indicates that HSA anticancer ferric complex compound is a potential way to improve the newly-developed anticancer drug. Meanwhile, the working mechanism of HSA anticancer ferric complex compound’s anticancer activity was also tentatively discussed.

The paper was co-authored by Prof. Yang and Prof. Zhang from School of Pharmacy, Nantong University, and Associate Prof. Wang Tao of SUSTech Biology Department. Their research received financial support from Ministry of Science and Technology of the People’s Republic of China and the National Natural Science Foundation of China.

Link for the paper: http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b00509