ABSTRACT Multiple DNA polymerases have been identified in multicellular eukaryotes, and recent investigations have revealed that eukaryotic cells contain at least fourteen types of DNA polymerase. To study in vivo roles of each of the DNA polymerases, a promising approach is to use DNA polymerase inhibitors, as tool and molecular probes to distinguish DNA polymerases and to clarify their biological and in vivo functions. We have widely screened such natural compounds, and succeeded to obtain many different types of novel DNA polymerase inhibitors, and in the process, we found that some of them, sulfoquinovosylacylglycerols (SQAG), could be clinically-promising immunosuppressive and/or anti-tumor agents. The purpose of this review is at first to introduce our studies of newly found DNA polymerase inhibitors, next to elucidate precise molecular action and medicinal application of SQAG based on three-dimensional structural model analysis and by comparison with the spatial positioning of specific amino acids binding to the inhibitors on the smallest polymerase, β. The studies can not only decipher the in vivo functions of each of the DNA polymerases, but also such approaches would make the molecular designs of new theoretically-ideal immunosuppressive or anti-tumor agents possible by computer simulation.
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