A new field of science, chemical biology/ chemical genetics/ chemical genomics (cb/cg/cg) has emerged since the late 1990's, especially in the United States. The NIH Roadmap agenda, Molecular Libraries Screening Center Network (MLSCN), became a drive force to push cb/cg/cg forward. Cb/cg/cg studies consist of three methodologies, chemical libraries with small molecules, high-throughput screenings, and computational databases. In this review, we focus on the importance of chemical libraries. Natural products-originated chemical libraries or their synthesized related compounds-derived chemical libraries have long contributed to human health sciences in mainly pharmaceutical industries. The reason why natural products have been of interest is that they consist of diverse and complex chemical compounds. This character makes natural compounds important as the seed of future medicine. Currently, pharmaceutical industry-based chemical biology using biology-oriented chemical libraries has spun off into the cb/cg/cg studies for basic biology in non-profit scientific organizations and a variety of developments have resulted from the use of chemical libraries with natural products. To overcome the diversity and complexity of nature-originated chemical compounds, a new concept of synthesizing small chemical compounds, Diversity-Oriented Synthesis (DOS), has been established by Harvard chemist, Stuart Schreiber in late 1990's. Using split-pool synthesizing methodology, small molecules produced by DOS make it possible for us to obtain compounds that span a wide chemical space. Here, we discuss cb/cg/cg studies applied to signal transduction, stem cell differentiation and small G-protein researches. All of these studies are conducted not only using biology-oriented libraries but also DOS-oriented libraries. Although cb/cg/cg is a relatively young science that aims the post-genome era sciences, it must bridge chemistry and biology not only in the academia but also in pharmaceutical industries.

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More than 36,000 open reading frames (ORFs) from the human genome were previously analyzed by the autocorrelation function of electric charge distribution, revealing the existence of many proteins with a charge periodicity of 28 residues (PCP28) (Ke et al., Jpn. J. Appl. Phys. 2007). The major component of PCP28 was located in the nucleus, and the nuclear PCP28 of ten vertebrate and seven invertebrate organisms were predicted with a novel software system (Sakiyama et al., CBI Journal 2007) for revealing the biological significance of nuclear PCP28. Retrieval of the features of the human nuclear PCP28 in Swiss-Prot revealed that almost 90% of nuclear PCP28 functions in transcriptional regulation, including hypothetical transcription factors. To study how nuclear PCP28 is increased in eukaryote genomes, we compared the number of all nuclear PCP28 in vertebrate and invertebrate genomes. The results showed that nuclear PCP28 is specifically increased in vertebrate genomes and that the ratio of other types of PCP28 is almost constant in all eukaryote genomes. These findings strongly suggest that nuclear PCP28 is an essential protein for vertebrate organisms.

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