<> <http://www.w3.org/2000/01/rdf-schema#comment> "The repository administrator has not yet configured an RDF license."^^<http://www.w3.org/2001/XMLSchema#string> .
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<https://discovery-pp.ucl.ac.uk/id/eprint/1544707> <http://purl.org/dc/terms/title> "Novel potential peptide therapeutics for tuberculosis therapy"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery-pp.ucl.ac.uk/id/eprint/1544707> <http://purl.org/ontology/bibo/abstract> "Despite the existence of vaccinations, diagnostic tools and treatments, tuberculosis\r\n(TB) prevalence is increasing because of the circulation of people and misuse of\r\nantibiotics, giving rise to growing numbers of drug resistant strains of\r\nMycobacterium tuberculosis. There is therefore a pressing need to look for new\r\nstrategies against TB, in the hope of finding new drugs with novel mechanisms of\r\nanti-tubercular action or ways to potentiate the activity of already existing drugs and\r\nreduce treatment duration.\r\nThis thesis explores the employment of peptides in anti-tuberculosis therapy. The\r\nproject was initiated by the identification of a novel therapeutic target in M.\r\ntuberculosis: murein peptide ligase (Mpl, Rv3712), an enzyme involved in the\r\nbacterial peptidoglycan recycling process. The aim is to synthesise its putative\r\nnatural substrates (peptidoglycan peptide fragments) to characterise its activity and\r\nsynthesise sequence analogues. These analogues were tested on the whole-cell\r\nand will be evaluated for inhibitory activity on the recombinant Mpl enzyme and\r\neventually could be used in combination with existing or new drugs to see whether\r\nthey increase anti-tubercular potency and thus combat resistance. Attainment of the\r\nputative substrate required the synthesis of mDAP, an unusual amino acid unique to\r\npeptidoglycan. Its synthesis was successfully completed and it was incorporated in\r\nthe tripeptide Mpl putative substrate.\r\nSolid-phase synthesis has been used successfully and proved effective for rapid\r\nsynthesis of multiple short peptide analogues in parallel. In addition it was used to\r\nsynthesise anti-tuberculosis lasso peptides, lariatins A and B, lassomycin and\r\nanalogues, to evaluate the structural requirements for biological activity.\r\nThe method for the heterologous expression and purification of recombinant Mpl\r\nfrom M. tuberculosis has been confirmed as successful, and the enzyme is available\r\nfor future target-based evaluation using the synthesised mDAP-containing tripeptide\r\nand eventually for other mDAP-containing PG fragments and analogues."^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery-pp.ucl.ac.uk/id/eprint/1544707> <http://purl.org/dc/terms/date> "2017-03-28" .
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