創薬指向型ケミカル・プロテオミクス

抄録

Looking back over the past decade one has the impression of rapid biological breakthroughs but of chemical design knowledge advancing at a slower pace. Therefore compound-oriented approach is really needed for drug discovery.
Current commercial available drugs are mainly synthetic small compounds, and at least in near future, still such small molecules will be dominated on the drug market. Some of these compounds cause specific phenotypes (drug effects) to cells/animals, although these mode-of-actions are unknown. Chemical proteomic process uses synthetic small compounds to make clear their mechanism or to study protein functions. In pharmaceutical industries, it is very important to generate lead compound-drug target pairs with pharmacological significance. There are two types of chemical proteomics. One is the protein expression-based profiling of synthetic compounds to discover marker proteins and to identify the pathway of drug actions. Another is the drug target identification by using proteome technology.
Recent developments of quantitative proteome analysis using stable isotopes have rendered the protein-expression profiling in human cell lines reliable and feasible to look into a drug response pathway. We have developed new software to make possible the automated quantitation and annotation from large scale- data.
For primary target elucidation, synthetic small compounds are covalently immobilized to solid-phase as affinity matrix and subsequently allow proteins identification as drug targets. But compared with natural products, the specificity of synthetic compounds to their protein targets is rather low in many cases. Thus, I will talk about the quantitative manner to discriminate specific binders from nonspecific interactions.