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Region Hovedstaden - en del af Københavns Universitetshospital
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Solid-phase synthesis of smac peptidomimetics incorporating triazoloprolines and biarylalanines

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DOI

  1. Characterization of genetic intratumor heterogeneity in colorectal cancer and matching patient-derived spheroid cultures

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Short-term spheroid culture of primary colorectal cancer cells as an in vitro model for personalizing cancer medicine

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Apoptotic induction mechanisms are of crucial importance for the general homeostasis of multicellular organisms. In cancer the apoptotic pathways are downregulated, which, at least partly, is due to an abundance of inhibitors of apoptosis proteins (IAPs) that block the apoptotic cascade by deactivating proteolytic caspases. The Smac protein has an antagonistic effect on IAPs, thus providing structural clues for the synthesis of new pro-apoptotic compounds. Herein, we report a solid-phase approach for the synthesis of Smac-derived tetrapeptide libraries. On the basis of a common (N-Me)AVPF sequence, peptides incorporating triazoloprolines and biarylalanines were synthesized by means of Cu(I)-catalyzed azide-alkyne cycloaddition and Pd-catalyzed Suzuki cross-coupling reactions. Solid-phase procedures were optimized to high efficiency, thus accessing all products in excellent crude purities and yields (both typically above 90%). The peptides were subjected to biological evaluation in a live/dead cellular assay which revealed that structural decorations on the AVPF sequence indeed are highly important for cytotoxicity toward HeLa cells.
OriginalsprogEngelsk
TidsskriftACS Combinatorial Science
Vol/bind13
Udgave nummer6
Sider (fra-til)667-75
Antal sider9
DOI
StatusUdgivet - 2011

ID: 33257393