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Click Chemistry Publications - Scripps Research Institute

The identification of new bioactive small molecules is increasingly reliant upon the synthesis and screening of chemical libraries. The extent of structural diversity and the proportion of unique scaffolds in a library are commonly acknowledged to be the most important factors in determining its success in identifying new biologically relevant compounds. Particularly important in this respect are macrocycles, which display unique physicochemical attributes and are used in many clinical applications. Despite these advantages, macrocycles remain under-represented in many contemporary screening collections, predominantly due to their synthetic intractability. Diversity-oriented­ synthesis is a powerful method for the construction of deliberately diverse collections of small molecules, and many research groups are working to apply its principles to the synthesis of structurally and functionally diverse macrocyclic libraries. In this short review we introduce why macrocycles are promising chemotypes in screening libraries, especially for challenging biological targets such as protein–protein interactions, and we review a collection of strategies developed in our laboratory for the diversity-oriented synthesis of macrocycle libraries. We analyse a selection of the macrocycle collections generated using these approaches and conclude with our perspective on future directions of the field.

The identification of new bioactive small molecules is increasingly reliant upon the synthesis and screening of chemical libraries. The extent of structural diversity and the proportion of unique scaffolds in a library are commonly acknowledged to be the most important factors in determining its success in identifying new biologically relevant compounds. Particularly important in this respect are macrocycles, which display unique physicochemical attributes and are used in many clinical applications. Despite these advantages, macrocycles remain under-represented in many contemporary screening collections, predominantly due to their synthetic intractability. Diversity-oriented­ synthesis is a powerful method for the construction of deliberately diverse collections of small molecules, and many research groups are working to apply its principles to the synthesis of structurally and functionally diverse macrocyclic libraries. In this short review we introduce why macrocycles are promising chemotypes in screening libraries, especially for challenging biological targets such as protein–protein interactions, and we review a collection of strategies developed in our laboratory for the diversity-oriented synthesis of macrocycle libraries. We analyse a selection of the macrocycle collections generated using these approaches and conclude with our perspective on future directions of the field.1 Introduction1.1 Chemical Libraries in Drug Discovery and Chemical Biology1.2 Macrocycles in Screening Collections1.3 Diversity-Oriented Synthesis2 Build/Couple/Pair2.1 Strategy Overview2.2 Typical B/C/P Strategies2.3 Advanced B/C/P Strategies2.4 Two-Directional Synthesis3 Alternative Approaches to Macrocycle Library Synthesis4 Discussion and Concluding Remarks

ThalesNano Nanotechology Inc - Publications

Small Molecules for Cancer Immunotherapy Conference

Courses of Study | IIT Gandhinagar

Beyond these commercialization projects, the vast majority of our ongoing work is best classified as basic research. We are learning how well we can make natural product stereoisomer libraries by fluorous mixture synthesis, discovering the ins and outs of asymmetric reactions of axially chiral amides, and looking into new analogs of the macrocyclic anticancer agent dictyostatin. The force motif behind all our work is a cadre of enthusiastic students and postdocs.

Prospective of 68Ga-Radiopharmaceutical Development

Prospective of 68 Ga-Radiopharmaceutical Development

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Molecules | April 2014 - Browse Articles


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