Document Detail


Isolation and synthesis of falcitidin, a novel myxobacterial-derived acyltetrapeptide with activity against the malaria target falcipain-2.
MedLine Citation:
PMID:  23340660     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  JOURNAL ARTICLE     Date:  2013-1-23
Journal Detail:
Title:  The Journal of antibiotics     Volume:  -     ISSN:  0021-8820     ISO Abbreviation:  J. Antibiot.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0151115     Medline TA:  J Antibiot (Tokyo)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
MerLion Pharmaceuticals, Singapore, Singapore.
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