Discovery of a new class of inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B by biology-oriented synthesis
Discovery of a new class of inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B by biology-oriented synthesis
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DOI：
10.1002/anie.200801566
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Waldmann, Herbert
中科院分区：
文献类型：
--
作者：
Noeren-Mueller, Andrea;Wilk, Wolfram;Waldmann, Herbert
The causative organism of pulmonary tuberculosis, Mycobacterium tuberculosis, secretes two eukaryote-like protein tyrosine phosphatases, MptpA and MptpB, which selectively dephosphorylate human host proteins involved in interferong signaling pathways, thereby preventing the initiation of host defense mechanisms.[1] The inhibition of these enzymes might prevent the proliferation of Mycobacterium tuberculosis in human host macrophages and therefore represents a promising strategy for the development of selective antibiotics against this severe pathogen.[2] As Mycobacterium tuberculosis is a major human pathogen, and as antibiotic-resistant strains spread rapidly, new chemotherapeutic approaches are urgently required.In the de novo development of structurally new enzyme inhibitors, the relevance of compound classes to nature is of particular importance. Natural products can be regarded as biologically prevalidated starting points for the generation of compound collections, as their underlying scaffolds were selected evolutionarily as suitable core structures for protein binding.[3, 4] We recently introduced a treelike structural
