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https://doi.org/10.1038/ja.2012.123
Title: | Isolation and synthesis of falcitidin, a novel myxobacterial-derived acyltetrapeptide with activity against the malaria target falcipain-2 |
Authors: | Somanadhan, B. Kotturi, S.R. Yan Leong, C. Glover, R.P. Huang, Y. Flotow, H. Buss, A.D. Lear, M.J. Butler, M.S. |
Keywords: | Chitinophaga Falcipain Falcitidin Malaria Myxobacteria Tetrapeptide |
Issue Date: | May-2013 |
Source: | Somanadhan, B., Kotturi, S.R., Yan Leong, C., Glover, R.P., Huang, Y., Flotow, H., Buss, A.D., Lear, M.J., Butler, M.S. (2013-05). Isolation and synthesis of falcitidin, a novel myxobacterial-derived acyltetrapeptide with activity against the malaria target falcipain-2. Journal of Antibiotics 66 (5) : 259-264. ScholarBank@NUS Repository. https://doi.org/10.1038/ja.2012.123 |
Abstract: | 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. © 2013 Japan Antibiotics Research Association All rights reserved. |
Source Title: | Journal of Antibiotics |
URI: | http://scholarbank.nus.edu.sg/handle/10635/76417 |
ISSN: | 00218820 |
DOI: | 10.1038/ja.2012.123 |
Appears in Collections: | Staff Publications |
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