LEADER 04174nam 22005775 450 001 9910298588103321 005 20200630074519.0 010 $a981-10-6623-X 024 7 $a10.1007/978-981-10-6623-8 035 $a(CKB)4100000001039681 035 $a(DE-He213)978-981-10-6623-8 035 $a(MiAaPQ)EBC5123074 035 $a(PPN)221247157 035 $a(EXLCZ)994100000001039681 100 $a20171103d2018 u| 0 101 0 $aeng 135 $aurnn|008mamaa 181 $ctxt$2rdacontent 182 $cc$2rdamedia 183 $acr$2rdacarrier 200 10$aDevelopment of Chemistry-Based Screening Platform for Access to Mirror-Image Library of Natural Products /$fby Taro Noguchi 205 $a1st ed. 2018. 210 1$aSingapore :$cSpringer Singapore :$cImprint: Springer,$d2018. 215 $a1 online resource (XIV, 80 p. 46 illus., 18 illus. in color.) 225 1 $aSpringer Theses, Recognizing Outstanding Ph.D. Research,$x2190-5053 311 $a981-10-6622-1 320 $aIncludes bibliographical references at the end of each chapters. 327 $aIntroduction -- Development of a Mirror-image Screening Process by Using Synthetic Proteins -- Synthesis of Grb2 SH2 Domain Proteins for Mirror-image Screening Systems -- Conclusions. 330 $aThis thesis mainly describes the development of a screening process for a mirror-image library of chiral natural products. It demonstrates how, by using mirror-image proteins for the screening of available natural products, unavailable mirror-image isomers of natural products can be screened in a mirror process. Moreover, as mirror-image isomers including target proteins and natural products are mainly prepared by means of chemical synthesis, the screening strategy presented here suggests the importance of organic chemistry. Natural products are commonly used as valuable resources for drug discovery. However, as they are mostly produced as single enantiomeric forms, researchers have tested only natural products bearing one stereochemistry available in nature. As natural products and their enantiomers have identical physicochemical properties and different biological activities, mirror-image isomers of natural products are promising candidates for novel medicinal resources. In an effort to identify anticancer agents from the mirror-image library, chemical protein syntheses of some target oncoproteins, MDM2, MDMX and Grb2, and their applications to the chemical array screening process were achieved. In the course of this process the NP843 enantiomer, which is the enantiomer of an ?-tocopherol derivative, was successfully identified as a novel MDM2-p53 interaction inhibitor. These results clearly show that a mirror-image library of chiral natural products represents an invaluable medicinal resource. Accordingly, the chemistry-based screening strategy described in this thesis will be of great interest to a broad range of chemists involved in natural product, medicinal, and synthetic chemistry. 410 0$aSpringer Theses, Recognizing Outstanding Ph.D. Research,$x2190-5053 606 $aPharmaceutical chemistry 606 $aChemistry, Organic 606 $aPharmaceutical technology 606 $aMedicinal Chemistry$3https://scigraph.springernature.com/ontologies/product-market-codes/C28000 606 $aOrganic Chemistry$3https://scigraph.springernature.com/ontologies/product-market-codes/C19007 606 $aPharmaceutical Sciences/Technology$3https://scigraph.springernature.com/ontologies/product-market-codes/B21010 615 0$aPharmaceutical chemistry. 615 0$aChemistry, Organic. 615 0$aPharmaceutical technology. 615 14$aMedicinal Chemistry. 615 24$aOrganic Chemistry. 615 24$aPharmaceutical Sciences/Technology. 676 $a572.36 700 $aNoguchi$b Taro$4aut$4http://id.loc.gov/vocabulary/relators/aut$0767865 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910298588103321 996 $aDevelopment of Chemistry-Based Screening Platform for Access to Mirror-Image Library of Natural Products$91563687 997 $aUNINA