| Isolation and synthesis of falcitidin, a novel myxobacterial-derived acyltetrapeptide with activity against the malaria target falcipain-2. | |
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MedLine Citation:
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PMID: 23340660 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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A 384-well microtitre plate fluorescence cleavage assay was developed to identify inhibitors of the cysteine protease falcipain-2, an important antimalarial drug target. Bioassay-guided isolation of a MeOH extract from a myxobacterium Chitinophaga sp. Y23 isolated from soil collected in Singapore, led to the identification of a new acyltetrapeptide, falcitidin (1), which displayed an IC(50) value of 6 μM against falcipain-2. The planar structure of 1 was secured by NMR and MS/MS analysis. Attempts to isolate further material for biological testing were hampered by inconsistent production and by a low yield (<100 μg l(-1)). The absolute configuration of 1 was determined by Marfey's analysis and the structure was confirmed through total synthesis as isovaleric acid-D-His-L-Ile-L-Val-L-Pro-NH(2). Falcitidin (1) is the first member of a new class of falcipain-2 inhibitors and, unlike other peptide-based inhibitors, does not contain reactive groups that irreversibly bind to active cysteine sites.The Journal of Antibiotics advance online publication, 23 January 2013; doi:10.1038/ja.2012.123. |
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Authors:
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Brinda Somanadhan; Santosh R Kotturi; Chung Yan Leong; Robert P Glover; Yicun Huang; Horst Flotow; Antony D Buss; Martin J Lear; Mark S Butler |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-23 |
Journal Detail:
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Title: The Journal of antibiotics Volume: - ISSN: 0021-8820 ISO Abbreviation: J. Antibiot. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0151115 Medline TA: J Antibiot (Tokyo) Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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MerLion Pharmaceuticals, Singapore, Singapore. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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