AsiaChem | Chemistry in Japan | December 2021 Volume 2 Issue 1

12 | December 2021 www.facs.website Hiroaki Suga Hiroaki Suga is a Professor of the Department of Chemistry, Graduate School of Science in the University of Tokyo. He received Ph.D. at MIT (1994) followed by post-doctoral fellow in MGH (1997). He was Assistant and tenured Associate Professor in the State University of New York, University at Buffalo (1997–2003) and Professor in the Research Center for Advanced Science and Technology in the University of Tokyo (2003–2010). Since 2010, he has the present position. He is the recipient of Akabori Memorial Award 2014, Max-Bergmann Medal 2016, Nagoya Medal Silver 2017, Vincent du Vigneaud Award 2019, Bohlmann Lecture 2019 and The Research Award of the Alexander von Humboldt Foundation 2020. He is also a co-founder of PeptiDream and MiraBiologics in Japan. Ata Abbas Ata Abbas was born and grew up in India. After receiving his MSc (organic chemistry) from Aligarh Muslim University, India, he worked for a pharmaceutical company for some time. He later went on to receive his PhD from Nanyang Technological University, Singapore in 2015. Currently he is a post-doctoral researcher in Suga lab at The University of Tokyo where his interests are new chemical reactions to diversify genetically encoded macrocyclic peptide libraries and RaPID mRNA display. He is particularly passionate about mild, water based chemistries that are applicable to biological systems. Display technology platforms offer their own unique set of challenges for chemical transformations, at the heart of which lies peptide macrocyclization. The amenable reactions for peptide macrocyclization on this platform need to meet a number of criteria like high reactivity, selectivity, mild conditions, irreversibility and in many cases, a unique requirement to be assimilated into the translation machinery. Skillful utilization of these reactions has led to the formation of huge macrocyclic peptide libraries with varied linkages and topographies which have in turn led to the discovery of a number of hits for purposes such as drug discovery and others. Herein, we review those reactions which have mainly been applied in mRNA and phage display and discuss their technical characteristics and significance. GENETICALLY ENCODED LIBRARIES of peptides are an inexhaustible repertoire of therapeutic entities. They, however, generally work better when cyclized. Cyclic peptides are known to have two major advantages over their linear counterparts. Firstly, they are more resistant to proteases1 and hence have longer half-lives and better bioavailability2 for application as drugs etc. Secondly, they are more compact, have lesser degrees of freedom and fewer available conformations due to which they bind more tightly to the target protein by saving on entropy cost.3 Moreover, they are indicated to possibly have better cell permeability than their linear counterparts. The development of methodologies applicable to peptide cyclization under mild conditions constitutes an important and active area of research. Such methodologies must fulfil the requirement of application to not only diverse sequences but Peptide Cyclization Methodologies Amenable to in Vitro Display By Hiroaki Suga and Ata Abbas https://doi.org/10.51167/acm00018

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