Leupeptazin, a highly modified tripeptide isolated from cultures of a Streptomyces sp. inhibits cathepsin K

Natasha Kruglyak; David E. Williams; Henry Chen; Simon Law; Jadwiga Kaleta; Ivan Villanueva; Julian E. Davies; Raymond J. Andersen; Dieter Brömme

doi:10.1016/j.bmcl.2017.02.007

Leupeptazin, a highly modified tripeptide isolated from cultures of a Streptomyces sp. inhibits cathepsin K

Natasha Kruglyak
, David E. Williams
, Henry Chen
, Simon Law
, Jadwiga Kaleta
, Ivan Villanueva
, Julian E. Davies
, Raymond J. Andersen
, Dieter Brömme

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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, K_i, of 44 μM.

Original language	English
Pages (from-to)	1397-1400
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	27
Issue number	6
DOIs	https://doi.org/10.1016/j.bmcl.2017.02.007
State	Published - 2017
Externally published	Yes

Keywords

Leupeptin
Protease inhibition
Streptomyces
Structure elucidation

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10.1016/j.bmcl.2017.02.007

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title = "Leupeptazin, a highly modified tripeptide isolated from cultures of a Streptomyces sp. inhibits cathepsin K",

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.",

keywords = "Leupeptin, Protease inhibition, Streptomyces, Structure elucidation",

author = "Natasha Kruglyak and Williams, \{David E.\} and Henry Chen and Simon Law and Jadwiga Kaleta and Ivan Villanueva and Davies, \{Julian E.\} and Andersen, \{Raymond J.\} and Dieter Br{\"o}mme",

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year = "2017",

doi = "10.1016/j.bmcl.2017.02.007",

language = "English",

volume = "27",

pages = "1397--1400",

journal = "Bioorganic and Medicinal Chemistry Letters",

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TY - JOUR

T1 - Leupeptazin, a highly modified tripeptide isolated from cultures of a Streptomyces sp. inhibits cathepsin K

AU - Kruglyak, Natasha

AU - Williams, David E.

AU - Chen, Henry

AU - Law, Simon

AU - Kaleta, Jadwiga

AU - Villanueva, Ivan

AU - Davies, Julian E.

AU - Andersen, Raymond J.

AU - Brömme, Dieter

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Leupeptin

KW - Protease inhibition

KW - Streptomyces

KW - Structure elucidation

UR - https://www.scopus.com/pages/publications/85013040485

U2 - 10.1016/j.bmcl.2017.02.007

DO - 10.1016/j.bmcl.2017.02.007

M3 - Article

C2 - 28228366

AN - SCOPUS:85013040485

SN - 0960-894X

VL - 27

SP - 1397

EP - 1400

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 6

ER -

Leupeptazin, a highly modified tripeptide isolated from cultures of a Streptomyces sp. inhibits cathepsin K

Abstract

Keywords

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