Medicinal Chemistry and Chemical Biology, Poster
MC-173
Synthetic Study of SUMO E2 Enzyme (Ubc9)
Y. Zhang1, S. Oishi1, J. W. Bode1,2*
1Institute of Transformative Bio-molecules (ITbM), Nagoya University, Japan, 2Laboratorium für Organische Chemie, ETH-Zürich, Zürich, Switzerland
SUMO E2 (Ubc9) is a conjugating enzyme for sumoylation, which is an important post-translational modification involved in distinct cellular processes ranging from cell-cycle progression to gene expression.1 To study its biological role, we aim to develop a rapid and efficient chemical synthetic strategy for Ubc9 and its derivatives with functional groups, such as photoaffinity probes.

Ubc9 is composed of 158 amino acids. Due to the size limitation of SPPS, we divided it into four segments (Scheme 1). These four segments will be assembled by the combination of the three current ligation method: serine and threonine ligation (STL),2 the α-ketoacid-hydroxylamine (KAHA) ligation3 and native chemical ligation (NCL).4 It will be the first time to combine the three ligation methods to synthesize a protein. Since these three ligation methods utilize different functional group partners, we hypothesize that these four peptide segments will be assembled in a controlled manner without tedious protection-deprotection steps, and Ubc9 will be efficiently synthesized. This rapid synthetic strategy will also enable us to produce different functionalized protein derivatives only by replacing one peptide segment with another.

In this poster session, we will report the progress of our total chemical synthesis of Ubc9.
[1] Kerscher, O., Felberbaum, R., Hochstrasser, M. Annu. Rev. Cell Dev. Biol. 2006, 22, 159.
[2] Zhang, Y., Xu C., Lam, H. Y., Proc. Natl. Acad. Sci. USA, 2013, 110, 6657.
[3] Rohrabacher, F., Wucherpfennig, T. G., Bode, J. W, Top. Curr. Chem., 2015, 363, 1.
[4] Dawson, P. E., Muir, T. W., Clarklewis, I., Kent, S. B. H., Science, 1994, 266, 776.