{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/379916"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/379916","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"Small molecule-degrader conjugates for MALAT1 triplex degradation","abstract":"Metastasis is the primary cause of death associated with oncological disease. However, the biological processes of metastasis still need to be fully rationalised and understood. The insurgence of secondary neoplasms for numerous types of cancer has been correlated multiple times to the overexpression of a specific, long non-coding RNA sequence called MALAT1. Due to its uncommon triple helix structure, this transcript has a noteworthy stability, with a half-life of up to 15 hours, resulting in its build-up in the cell environment. This work details my efforts in the design and synthesis of efficient small molecule drugs based on the PINAD (Proximity Induced Nucleic Acid Degrader) technology for the selective targeting and cleavage of the uncommon secondary triple helix structure found at the 3’ end of human MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) RNA transcript. Taking advantage of the peculiar architecture composing the ENE+A tract of MALAT1, we prepared a small molecule that targets this transcript with an elevated level of selectivity due to its duplicitous nature of conjugate merging a MALAT1 specific binder and an imidazole-based warhead for RNA degradation. 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This work details my efforts in the design and synthesis of efficient small molecule drugs based on the PINAD (Proximity Induced Nucleic Acid Degrader) technology for the selective targeting and cleavage of the uncommon secondary triple helix structure found at the 3’ end of human MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) RNA transcript. Taking advantage of the peculiar architecture composing the ENE+A tract of MALAT1, we prepared a small molecule that targets this transcript with an elevated level of selectivity due to its duplicitous nature of conjugate merging a MALAT1 specific binder and an imidazole-based warhead for RNA degradation. 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Taking advantage of the peculiar architecture composing the ENE+A tract of MALAT1, we prepared a small molecule that targets this transcript with an elevated level of selectivity due to its duplicitous nature of conjugate merging a MALAT1 specific binder and an imidazole-based warhead for RNA degradation. 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