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Books > Science & Mathematics > Biology, life sciences > Biochemistry
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Development of Chemistry-Based Screening Platform for Access to Mirror-Image Library of Natural Products (Hardcover, 1st ed. 2018)
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Development of Chemistry-Based Screening Platform for Access to Mirror-Image Library of Natural Products (Hardcover, 1st ed. 2018)
Series: Springer Theses
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This 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 o nly 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.
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