Bulletin Number Four 1985

The antigenic determinants o f these proteins are o f particular interest since their clinical use is likely to be lim ited by immunological side-effects such as hypersensitivity. It is fortunate that trichosanthin and α - and β -momorcharin show great promise as clinical alternatives since both proved to be immu­ nogenic, but the value o f the whole class o f proteins would increase i f a large set o f non-cross-reacting species were available. A promising route to achieving such an end would be to use the frontier techniques o f genetic engineering and protein engineering. The available antibodies would be used to identify those parts o f the plants most active in synthesizing these proteins. From this region mRNA would be extracted and used to prepare a cDNA bank. The cDNA bank would be screened w ith synthetic radioactive oligonucleotide probes, encoding appropriate regions o f the amino acid sequences, and relevant clones sequenced by Sanger's ‘dideoxy technique' after subcloning into M13 phage. It is then relatively easy to make mutations in vitro that w ill allow intelligent replacements o f any amino acid , based on a known tertiary structure. Con structions in 'expression vectors' can then be made to allow high-level synthesis o f the mutant proteins in E. coli or yeast. In this way the antigenic determinants could be varied at w ill once they were identified. Monoclonal Antibody Production *Drs. W.K.K. Ho & K.N. Leung , Department o f Biochemistry Monoclonal antibodies are antibodies produced by cloning hybrid cells originally prepared in vitro where a normal antibody-producing cell is fused w ith a cancerous cell. Using this technique, a cell line capable o f producing a specific and homogenous population o f antibody can be obtained. Contrary to the conventional system o f antibody production, this technique can theoretically produce an unlimited supply o f highly pure antibodies as long as the original cell line is preserved. The short-term goal o f our research in this direction is to establish techniques for raising highly specific monoclonal antibodies. In the long range, we aim to expand our work into the area o f biomedical assays. Examples o f future developments may include: radioimmunoassay, enzyme-linked immunoassay and histoimmunoassay. Our current project is to raise monoclonal antibodies against the opiate receptor and a serum protein called Apo B48. These two projects are carried out more for academic interest than for their applied value. Nevertheless, since we are more familiar w ith these systems, we hope the insights gained from these studies would enable us to extend to other fields which have greater commercial value. Projects which we are planning to develop in the field o f clinical diagnosis include the raising o f monoclonal antibodies against different types o f human tumours, drugs and bacterial antigens. In this respect, originality would not be our primary concern. Our goal is to produce antibodies which can be devel oped into immunoassay for the diagnosis o f diseases. ( 2) Other Biochemical Research Research Programme for the Isolation o f Fertility Regulating Agents from Plants —Y.C. Kong As a founding member o f the 'Multicentred Collaborative Research Programme for the Isolation o f Fe rtility Regulating Agents from Plants', the Biochemistry Department has made significant break throughs in this eight-year old international research programme sponsored by the World Health Organiz ation, Special Programme o f Research, Development and Research Training in Human Reproduction. On 25th January, 1985 , the Biochemistry Department and WHO together hosted a one-day symposium on campus under the title 'The Development o f New F e rtility Regulating Agents from Plants'. The Pro gramme, its logistic approach, methodology and recent results, were presented to an audience o f 150 scientists from the local and overseas academic and professional communities. The highlight o f the Symposium was our first public announcement o f the discovery and synthesis o f yuehchukene, a novel bis-indole alkaloid isolated from a local plant, Murraya paniculata. Yuehchukene showed potent anti-implantation activity in animal tests. It is now synthesized in bulk and subjected to in-depth phar macological evaluation. Patents for the use o f yuehchukene in fe rtility regulation and its synthesis process are being filed. In the 13th Annual Report (1984) o f WHO Special Programme in Human Repro duction, this discovery was hailed as the most ad vanced lead in the collaborative research programme. The discovery o f yuehchukene offers a new dimension to human fe rtility regulation hitherto dominated by the use o f steroidal pills. Being a natural product and acting post-coitally by the oral route, yuehchukene has every promise o f wide-spread social acceptability that transcends the present lim itation such as education o f recipients, cost o f administration and delivery and technical know-how in production. On the academic front, the in tro ­ duction o f a new drug calls for massive intellectual input to investigate its mode o f action, pharmacol­ ogical profile, physiological sequelae and finally its RECENT DEVELOPMENTS 23

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