Documents
-
- Full text
- closed access
-
- Download
- Title page_Table of contents
- open access
-
- Download
- Chapter 1 General introduction
- open access
-
- Download
- Chapter 3
- open access
- Full text at publishers site
-
- Download
- Chapter 4
- open access
- Full text at publishers site
-
- Chapter 5
- closed access
- Full text at publishers site
-
- Download
- Chapter 9 Summary and future perspectives
- open access
-
- Download
- Summary in Chinese
- open access
-
- Download
- Curriculum Vitae_List of publications
- open access
-
- Download
- Propositions+Acknowledgements
- open access
In Collections
This item can be found in the following collections:
Discovery and development of inhibitors selective for human constitutive proteasome and immunoproteasome active sites
This thesis describes the design and development of subunit‐selective inhibitors of particular
catalytically active subunits of human constitutive proteasomes and immunoproteasomes.
Most existing proteasome inhibitors are oligopeptides composed of 2‐4 amino acid residues,
N‐terminally capped and with the C‐terminus adapted to give an electrophilic trap. Such
compounds are also at the basis of the research described in this Thesis. Attention was
directed to substitute specific amino acid residues by either synthetic, non‐canonical amino
acid derivatives (with a review on the synthesis of such items given in Chapter 2) or dipeptide
isosteres. Alternatively, modifications of the electrophilic trap, specifically, the epoxyketone
moiety, were investigated. In this way, and by the synthesis of focused libraries, in which in
each case a number of structural analogues, rather than a...
This thesis describes the design and development of subunit‐selective inhibitors of particular
catalytically active subunits of human constitutive proteasomes and immunoproteasomes.
Most existing proteasome inhibitors are oligopeptides composed of 2‐4 amino acid residues,
N‐terminally capped and with the C‐terminus adapted to give an electrophilic trap. Such
compounds are also at the basis of the research described in this Thesis. Attention was
directed to substitute specific amino acid residues by either synthetic, non‐canonical amino
acid derivatives (with a review on the synthesis of such items given in Chapter 2) or dipeptide
isosteres. Alternatively, modifications of the electrophilic trap, specifically, the epoxyketone
moiety, were investigated. In this way, and by the synthesis of focused libraries, in which in
each case a number of structural analogues, rather than a single one, inhibitors selective for
β5c, β2c and β2i were discovered, and a number of two‐step activity‐based probes for probing
these activities in vitro and in situ were identified.
- All authors
- Xin, B.
- Editor(s)
- Xin B.
- Supervisor
- Overkleeft, H.S.; Marel, G.A. van der
- Co-supervisor
- Florea, B.I.
- Committee
- Ovaa, H.; Brouwer, J.; Süssmuth, R.; Stelt, M van der; Bonger, K.
- Qualification
- Doctor (dr.)
- Awarding Institution
- Leiden Institute of Chemistry (LIC) , Science , Leiden University
- Date
- 2017-09-27