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Development of Chemistry-Based Screening Platform for Access to Mirror-Image Library of Natural Products de Taro Noguchi

Development of Chemistry-Based Screening Platform for Access to Mirror-Image Library of Natural Products: Springer Theses

Autor Taro Noguchi
en Limba Engleză Hardback – 16 noi 2017
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 α-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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Specificații

ISBN-13: 9789811066221
ISBN-10: 9811066221
Pagini: 74
Ilustrații: XIV, 80 p. 46 illus., 18 illus. in color.
Dimensiuni: 155 x 235 mm
Greutate: 0.31 kg
Ediția:1st ed. 2018
Editura: Springer Nature Singapore
Colecția Springer
Seria Springer Theses

Locul publicării:Singapore, Singapore

Cuprins

Introduction.- Development of a Mirror-image Screening Process by Using Synthetic Proteins.- Synthesis of Grb2 SH2 Domain Proteins for Mirror-image Screening Systems.- Conclusions.

Textul de pe ultima copertă

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 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 α-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.

Caracteristici

Nominated as an outstanding Ph.D. thesis by Kyoto University Describes a pioneering chemistry-based screening process for drug discovery Provides valuable insights for the field of organic chemistry, especially regarding the total synthesis of natural products and proteins Includes supplementary material: sn.pub/extras