Bulletin Autumn‧Winter 1996

Resea r ch p r o j e c t s o n t he f u n c t i o n s a n d me c h a n i sms o f t r i c h o s a n t h i n Project title Year Amount received Investigators Molecular Cloning of α -momorcharin 1987 HK$50,000 Dr. P.C. Shaw, and Prof. W.K.K. Ho Protein Engineering of Trichosanthin and α -momorcharin ： Molecular Cloning and Expression 1989 HK$610,000 Dr. P.C. Shaw, Prof. W.K.K. Ho, and Dr. H.W. Yeung Protein Engineering of Trichosanthin and α -momorcharin ： Modification of Antigenic Determinants and Structure-function Studies 1991 HK$2,290,000 Dr. P.C. Shaw, Prof. W.K.K. Ho, Dr. Y.S. Moon, Dr. H.W. Yeung, Prof. T.B. Ng, and *Dr. H.W. Leung Trichosanthin Derivatives with Reduced Immunogenicity and Nephrotoxicity and Long Plasma Half-life 1995 HK$581,000 Dr. P.C. Shaw, and Prof. M.S.C. Tarn * Baptist University staff showed that the symptoms of AIDS i n certain patients were alleviated by th e protein. Thi s discovery aroused great international interest and provided a fresh impetus for research on trichosanthin at The Chinese University. As protein is made up of amino acids, an understanding of the latter's functions is crucial to the understanding of the protein's mechanisms. In order to learn the roles of different amino acids in the biochemical activities of trichosanthin and to identify those that trigger off antibody production, the researchers acquired a silicon graphic workstation with high processing power for manipulating large proteins in real time. Dr. Y.S. Moon of the CUHK Department of Computer Science and Engineering an d Dr. H.W. Leung from Baptist University helped set up the workstation and input information. Assistance was also obtained from Prof. Y.C. Dong of the Institute of Biophysics of the Academia Sinica in Beijing to elucidate the t h r e e - d i me n s i o n a l structures o f trichosanthin and α -momorcharin. Prof . Dong spent six months at the University, during whic h he used the workstation to draw three-dimensional models of the interactions between the two proteins and their targets. The models help identify the amino acids that are crucial to the functions of trichosanthin as well as those that cause side effects. Researchers were able to change ce r t a i n DNA sequences of t r i c ho s an t h i n and reinsert t hem i n t o Escherichia coli to obtain modified versions of the protein. Prof. Y.B. Ke and Mr. S.K. Ma, both experts i n trichosanthin from the Shanghai Institute of Cell Biology of th e Academia Sinica, helped the researchers develop a new assay system for studying the effects of the modified trichosanthin. The effects of the modified proteins on various biological systems were studied by Prof. T.B. Ng (Department o f Biochemistry) and Prof. W.Y. Chan (Department of Anatomy) at CUHK. Some of the modified proteins were given to Prof. Dong for three-dimensional analysis in Beijing. The joint efforts of these scientists resulted in publications in prestigious journals, such as Science in China and Journal of European Biochemistry. Trichosanthin — The Ancient Remedy Reveals Additional Modern Uses 23