Leupeptazin,a highly modified tripeptide isolated from cultures of a Streptomyces sp. inhibits cathepsin K |
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| Authors: | Natasha Kruglyak David E Williams Henry Chen Simon Law Jadwiga Kaleta Ivan Villanueva Julian E Davies Raymond J Andersen Dieter Brömme |
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| Institution: | 1. Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada;2. Departments of Chemistry and Earth, Ocean & Atmospheric Sciences, University of British Columbia, 2207 Main Mall, Vancouver, British Columbia V6T 1Z4, Canada;3. Department of Oral, Biological and Medical Sciences, University of British Columbia, 2151 Westbrook Mall, Vancouver, British Columbia V6T 1Z3, Canada;4. Department of Microbiology and Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada;5. Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada;6. Present address: Department of Biochemistry, University of Toronto, 101 College St, TMDT 5-401, Toronto, Ontario M5G 1L7, Canada |
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| Abstract: | Using a human cathepsin K-targeting inhibitor screen, a new leupeptin analogue, leupeptazin (1), containing an unprecedented piperidinotriazine moiety, was isolated from a liquid culture of soil Streptomyces sp. IS2-4 collected in northern Italy. The structure of leupeptazin was established using HRESIMS as well as 1D and 2D NMR data. The inhibitory activity of the compound towards the collagenase cathepsin K was tested in vitro to reveal moderate activity with an inhibition constant, Ki, of 44 μM. |
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| Keywords: | Streptomyces Leupeptin Protease inhibition Structure elucidation |
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