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SUMMARY:New Methods for the Chemical Synthesis of Post-Translationally Mod
 ified Peptides and Proteins
DTSTART:20241126T161500
DTEND:20241126T171500
DTSTAMP:20260429T100801Z
UID:ba9df015a37f9d00958fe4c50a4e167b46da53e545039f163c01074c
CATEGORIES:Conferences - Seminars
DESCRIPTION:Nina Hartrampf (University of Zurich)\nMany proteins and pepti
 dic natural products carry post-translational modifications (PTMs)\, which
  modulate their structure and function. Studying those modifications on a 
 molecular level requires unique and defined PTM patterns\, which can be ob
 tained through chemical peptide and protein synthesis. Shorter peptides ca
 n be obtained through traditional solid phase peptide synthesis (SPPS) in 
 batch. Flow-SPPS\, however\, often enables the routine synthesis of longer
  peptides and can additionally give additional insights to SPPS itself.[1]
 \n\nWe will first present the chemoenzymatic synthesis of lasso peptide Mc
 cJ25 and derivatives thereof.[2] Flow-SPPS of chemically modified precurso
 r peptides (57 amino acids)\, followed by in vitro transformation with rec
 ombinant maturation enzymes yielded an array of lasso peptides including p
 reviously inaccessible side chain and backbone modifications. This rapid a
 ccess to chemically modified lasso peptides could be used to investigate s
 tructure–activity relationships\, epitope grafting\, and the improvement
  of therapeutic properties.\nNot only peptides\, but also proteins can be 
 modified by PTMs. The protein MYC is an intrinsically disordered transcrip
 tion factor that is upregulated in >50% of cancers and engages in numerous
  protein-protein interactions. These interactions are often regulated thro
 ugh posttranslational modifications (PTMs) within MYC’s transactivation 
 domain (TAD)\, most commonly (poly)phosphorylation. In the second part of 
 this presentation\, our work on deciphering MYC’s phosphorylation-depend
 ent protein-protein interactions will be presented.[3] A first step toward
 s this goal was the synthesis of MYC’s TAD\, a so-called “difficult se
 quence”\, that is challenging to synthesize and therefore inspired the d
 evelopment of new generally applicable tools for chemical protein synthesi
 s.[4]\n\n\n[1]     N. Hartrampf\, A. Saebi\,‡ M. Poskus\,‡ Z. P. G
 ates\, A. J. Callahan\, A. E. Cowfer\, S. Hanna\, S. Antilla\, C. K. Schis
 sel\, A. J. Quartararo\, X. Ye\, A. J. Mijalis\, M. D. Simon\, A. Loas\, S
 . Liu\, C. Jessen\, T. E. Nielsen\, B. L. Pentelute\, Science 2020\, 368\,
  980–987. \n[2]     K. Schiefelbein\, J. Lang\, M. Schuster\, C. E. 
 Grigglestone\, R. Striga\, L. Bigler\, M. C. Schuman\, O. Zerbe\, Y. Li\, 
 N. Hartrampf\; J. Am. Chem. Soc. 2024\, 146 (25)\, 17261–17269.\n[3]  
    E. T. Williams\, K. Schiefelbein\, M. Schuster\, I. M. M. Ahmed\, M. 
 De Vries\, R. Beveridge\, O. Zerbe\, N. Hartrampf\; Chem. Sci. 2024\, 15\,
  8756–8765.\n[4]     H. Bürgisser\,‡ E. T. Williams\,‡ A. Jeandi
 n\, R. Lescure\, A. Premanand\, S. Wang\, N. Hartrampf\, J. Am. Chem. Soc.
  2024\, just accepted.\n 
LOCATION:CE 1 5 https://plan.epfl.ch/?room==CE%201%205
STATUS:CONFIRMED
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