Synthetic tools to study ubiquitin biology

Shahul Hameed, D.A. (2020)

Doctoral Thesis

Ubiquitin (Ub) is a small post-translational modifier protein involved in a myriad of biochemical processes including DNA damage repair, proteasomal proteolysis, and cell cycle control. Ubiquitin signalling pathways have not been completely deciphered due to the complex nature of the enzymes involved in ubiquitin conjugation and deconjugation. Hence, probes and assay reagents are important to get a better understanding of this pathway. Recently, improvements have been made in synthesis procedures of Ub derivatives. In this perspective, we explain various research reagents available and how chemical synthesis has made an important contribution to Ub research.

• Ubiquitin
• Solid Phase Peptide Synthesis
• Native Chemical Ligation
• Organic Synthesis
• Nuclear Magnetic Resonance
• Metal chelators
• Cell penetrating peptides
• cyclic peptide inhibitors
• 26S proteasome

• All authors: Shahul Hameed, D.A.
• Supervisor: Ovaa, H.; Neefjes, J.J.C.
• Co-supervisor: Sapmaz, A.
• Committee: Leeuwen, F. van; Martin, N.; Dijke, P. ten; Vermeulen, M.; Hoeben, R.C.; Kasteren, S.I. van; Heitman, L.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center [LUMC], Leiden University
• Date: 2020-06-23
• ISBN (print): 9789464021424
• Sponsorship: The work was financially supported by funding from Ubicode, the Dutch Research Council (NWO) and Oncode Institute. The printing costs were reimbursed by the LUMC, Leiden and the NKI, Amsterdam.