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SUMMARY:CANCELLED: LMB Seminar: New therapeutic modalities based on pseudo
 -natural peptides\, products\, and neobiologics - Prof. Hiroaki Suga\, Ph.
 D\, The University of Tokyo\, Graduate School of Science\, Department of C
 hemistry
DTSTART:20240226T110000Z
DTEND:20240226T120000Z
UID:TALK207406@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Hiroaki Suga is a Professor of the Department of Chemistry\, G
 raduate School of Science in the University of Tokyo. He received his Bach
 elor of Engineering (1986) and Master of Engineering (1989) from Okayama U
 niversity\, and Ph. D. in Chemistry (1994) from the Massachusetts Institut
 e of Technology. After three years of post-doctoral work in Massachusetts 
 General Hospital\, he became Assistant Professor in the Department of Chem
 istry in the State University of New York at Buffalo (1997) and promoted t
 o the tenured Associate Professor (2002). In 2003\, he moved to the Resear
 ch Center for Advanced Science and Technology in the University of Tokyo. 
 In 2010\, he changed his affiliation to the Department of Chemistry\, Grad
 uate School of Science. He is the recipient of Akabori Memorial Award 2014
 \, Japanese Peptide Society\, Max-Bergmann Gold Medal 2016\, Vincent du Vi
 gneaud Award 2019\, The Research Award of the Alexander von Humboldt Found
 ation 2020\, MIT T.Y. Shen Lectureship 2022\, ETHZ Prelog Medal Lecture 20
 22\, Wolf Prize in Chemistry 2023 and others. He is also a founder of Pept
 iDream Inc. Tokyo\, a publicly traded company in the Tokyo stock market\, 
 having many partnerships with pharmaceutical companies in worldwide. He is
  also a founder of MiraBiologics Inc. since 2017\n\nIntroduction\nMacrocyc
 lic peptides possess a number of pharmacological characteristics distinct 
 from other well-established therapeutic molecular classes\, resulting in a
  versatile drug modality with a unique profile of advantages. Macrocyclic 
 peptides are accessible by not only chemical synthesis but also ribosomal 
 synthesis. Particularly\, recent inventions of the genetic code reprogramm
 ing integrated with an in vitro display format\, referred to as RaPID (Ran
 dom non-standard Peptides Integrated Discovery) system\, have enabled us t
 o screen mass libraries (>1 trillion members) of non-standard peptides con
 taining multiple non-proteinogenic amino acids\, giving unique properties 
 of macrocyclic pseudo-natural peptides distinct from conventional peptides
 \, e.g. greater proteolytic stability\, higher affinity (low nM to sub nM 
 dissociation constants similar to antibodies)\, and superior pharmacokinet
 ics. The field is rapidly growing evidenced by increasing interests from i
 ndustrial sectors\, including mega-pharmas\, toward drug development effor
 ts on macrocyclic peptides as a new modality group. This lecture discusses
  their screening by the RaPID system\, and several showcases of therapeuti
 c potentials of such molecules. This lecture also discusses the most recen
 t advance in the display of pseudo-natural products generated by thiopepti
 de’s post-translationally modifying enzymes and the development of neobi
 ologics using LassoGraft technology based on the macrocyclic peptide pharm
 acophore sequences.\n\nReferences\n"Designing receptor agonists with enhan
 ced pharmacokinetics by grafting macrocyclic peptides into fragment crysta
 llizable regions." K. Sakai\; N. Sugano-Nakamura\; E. Mihara\; N.M. Rojas-
 Chaverra\; S. Watanabe\; H. Sato\; R. Imamura\; D.C. Voon\; I. Sakai\; C. 
 Yamasaki\; C. Tateno\; M. Shibata\; H. Suga\; J. Takagi\; K. Matsumoto\, N
 at. Biomed. Eng.\, (2022)\n"Lasso-grafting of macrocyclic peptide pharmaco
 phores yields multi-functional proteins."\nE. Mihara\; S. Watanabe\; N.K. 
 Bashiruddin\; N. Nakamura\; K. Matoba\; Y. Sano\; R. Maini\; Y. Yin\; K. S
 akai\; T. Arimori\; K. Matsumoto\; H. Suga*\; J. Takagi\, Nature communica
 tions\, 12\, 1543 (2021)\n"Ribosomal Elongation of Aminobenzoic Acid Deriv
 atives." T. Katoh\; H. Suga*\; Journal of the American Chemical Society\, 
 142\, 16518-16522 (2020) \n"GTP-State-Selective Cyclic Peptide Ligands of 
 K-Ras(G12D) Block Its Interaction with Raf." Z. Zhang\; R. Gao\; Q. Hu\; H
 . Peacock\; D.M. Peacock\; S. Dai\; K.M. Shokat\; H. Suga* ACS Cent. Sci.\
 , (2020) \n“Development of cyclic peptides with potent in vivo osteogeni
 c activity through RaPID-based affinity maturation” N. K. Bashiruddin\; 
 M. Hayashi\; M. Nagano\; Y. Wu\; Y. Matsunaga\; J. Takagi\; T. Nakashima\;
  H. Suga*\; Proceedings of the National Academy of Sciences USA 117 (49) 3
 1070-31077 (2020) \n“Ribosomal synthesis and de novo discovery of bioact
 ive foldamer peptides containing cyclic β-amino acids” T. Katoh\; T. Se
 ngoku\; K. Hirata\; K. Ogata\; H. Suga*\; Nature Chemistry 12\, 1081-1088 
 (2020) \n"Macrocyclic peptide-based inhibition and imaging of hepatocyte g
 rowth factor"K. Sakai\; T. Passioura\; H. Sato\; K. Ito\; H. Furuhashi\; M
 . Umitsu\; J. Takagi\; Y. Kato\; H. Mukai\; S. Warashina\; M. Zouda\; Y. W
 atanabe\; S. Yano\; M. Shibata\; H. Suga*\; K. Matsumoto\; Nature Chemical
  Biology\, 15\, 598-606 (2019) \nM. Nawatha\; J.M. Rogers\; S.M. Bonn\; I.
  Livneh\; B. Lemma\; S.M. Mali\; G.B. Vamisetti\; H. Sun\; B. Bercovich\; 
 Y. Huang\; A. Ciechanover\; D. Fushman\; H. Suga*\; A. Brik\; "De novo mac
 rocyclic peptides that specifically modulate Lys48-linked ubiquitin chains
 ." Nature Chemistry\, 11(7):644-652 (2019) 
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