A Structural and Functional Analogue of a Bowman Birk-type Protease Inhibitor from Odorrana Schmackeri

Yuxin Wu; Qilin Long; Ying Xu; Shaodong Guo; Tianbao Chen; Lei Wang; Mei Zhou; Yingqi Zhang; Chris Shaw; Brian Walker

doi:10.1042/BSR20160593

A Structural and Functional Analogue of a Bowman Birk-type Protease Inhibitor from Odorrana Schmackeri

Yuxin Wu, Qilin Long, Ying Xu, Shaodong Guo, Tianbao Chen, Lei Wang, Mei Zhou, Yingqi Zhang, Chris Shaw, Brian Walker

School of Pharmacy

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

12 Citations (Scopus)

238 Downloads (Pure)

Abstract

Frog skin secretions contain complex peptidomes and peptidic protease inhibitors are one of the biologically- and structurally-described groups of components. In this study, by use of molecular “shotgun” cloning and LC MS/MS fractionation sequencing, a novel Bowman Birk-type heptadecapeptide (AALKGCWTKSIPPKPCF-amide), named OSTI, with a canonical Cys6-Cys16 disulfide bridge, was isolated and identified in Piebald Odorous Frog (Odorrana schmackeri) skin secretion. A synthetic replicate of OSTI exhibited trypsin inhibitory activity with a Ki value of 0.3 ± 0.04 nM and also a tryptase inhibitory effect with a Ki of 2.5 ± 0.6 μM. This is the first time that this property has been reported for a peptide originating from amphibian sources. In addition, substituting lysine (K) with phenylalanine (F) at the presumed P1 position, completely abrogated the trypsin and tryptase inhibition, but produced a strong chymotrypsin inhibition with a Ki of 1.0 ± 0.1 μM. Thus, the specificity of this peptidic protease inhibitor could be optimized through modifying the amino acid residue at the presumed P1 position and this novel native OSTI, along with its analogue, [Phe9]-OSTI, have expanded the potential drug discovery and development pipeline directed towards alleviation of
serine protease-mediated pathologies.

Original language	English
Journal	Bioscience Reports
Volume	37
Issue number	2
Early online date	28 Apr 2017
DOIs	https://doi.org/10.1042/BSR20160593
Publication status	Published - Apr 2017

Keywords

Skin secretion. Molecular cloning. Bowman Birk inhibitor. Peptide. Tryptase.

Access to Document

10.1042/BSR20160593Licence: CC BY

A structural and functional analogue of a Bowman–Birk-type protease inhibitor from Odorrana schmackeri
Copyright 2017 The Author(s). This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 2.18 MBLicence: CC BY

Fingerprint Dive into the research topics of 'A Structural and Functional Analogue of a Bowman Birk-type Protease Inhibitor from Odorrana Schmackeri'. Together they form a unique fingerprint.

Cite this

@article{df218489417142238f7fc6e61b8bce9a,

title = "A Structural and Functional Analogue of a Bowman Birk-type Protease Inhibitor from Odorrana Schmackeri",

abstract = "Frog skin secretions contain complex peptidomes and peptidic protease inhibitors are one of the biologically- and structurally-described groups of components. In this study, by use of molecular “shotgun” cloning and LC MS/MS fractionation sequencing, a novel Bowman Birk-type heptadecapeptide (AALKGCWTKSIPPKPCF-amide), named OSTI, with a canonical Cys6-Cys16 disulfide bridge, was isolated and identified in Piebald Odorous Frog (Odorrana schmackeri) skin secretion. A synthetic replicate of OSTI exhibited trypsin inhibitory activity with a Ki value of 0.3 ± 0.04 nM and also a tryptase inhibitory effect with a Ki of 2.5 ± 0.6 μM. This is the first time that this property has been reported for a peptide originating from amphibian sources. In addition, substituting lysine (K) with phenylalanine (F) at the presumed P1 position, completely abrogated the trypsin and tryptase inhibition, but produced a strong chymotrypsin inhibition with a Ki of 1.0 ± 0.1 μM. Thus, the specificity of this peptidic protease inhibitor could be optimized through modifying the amino acid residue at the presumed P1 position and this novel native OSTI, along with its analogue, [Phe9]-OSTI, have expanded the potential drug discovery and development pipeline directed towards alleviation ofserine protease-mediated pathologies.",

keywords = "Skin secretion. Molecular cloning. Bowman Birk inhibitor. Peptide. Tryptase.",

author = "Yuxin Wu and Qilin Long and Ying Xu and Shaodong Guo and Tianbao Chen and Lei Wang and Mei Zhou and Yingqi Zhang and Chris Shaw and Brian Walker",

year = "2017",

month = apr,

doi = "10.1042/BSR20160593",

language = "English",

volume = "37",

journal = "Bioscience Reports",

issn = "0144-8463",

publisher = "Portland Press Ltd.",

number = "2",

}

TY - JOUR

T1 - A Structural and Functional Analogue of a Bowman Birk-type Protease Inhibitor from Odorrana Schmackeri

AU - Wu, Yuxin

AU - Long, Qilin

AU - Xu, Ying

AU - Guo, Shaodong

AU - Chen, Tianbao

AU - Wang, Lei

AU - Zhou, Mei

AU - Zhang, Yingqi

AU - Shaw, Chris

AU - Walker, Brian

PY - 2017/4

Y1 - 2017/4

N2 - Frog skin secretions contain complex peptidomes and peptidic protease inhibitors are one of the biologically- and structurally-described groups of components. In this study, by use of molecular “shotgun” cloning and LC MS/MS fractionation sequencing, a novel Bowman Birk-type heptadecapeptide (AALKGCWTKSIPPKPCF-amide), named OSTI, with a canonical Cys6-Cys16 disulfide bridge, was isolated and identified in Piebald Odorous Frog (Odorrana schmackeri) skin secretion. A synthetic replicate of OSTI exhibited trypsin inhibitory activity with a Ki value of 0.3 ± 0.04 nM and also a tryptase inhibitory effect with a Ki of 2.5 ± 0.6 μM. This is the first time that this property has been reported for a peptide originating from amphibian sources. In addition, substituting lysine (K) with phenylalanine (F) at the presumed P1 position, completely abrogated the trypsin and tryptase inhibition, but produced a strong chymotrypsin inhibition with a Ki of 1.0 ± 0.1 μM. Thus, the specificity of this peptidic protease inhibitor could be optimized through modifying the amino acid residue at the presumed P1 position and this novel native OSTI, along with its analogue, [Phe9]-OSTI, have expanded the potential drug discovery and development pipeline directed towards alleviation ofserine protease-mediated pathologies.

AB - Frog skin secretions contain complex peptidomes and peptidic protease inhibitors are one of the biologically- and structurally-described groups of components. In this study, by use of molecular “shotgun” cloning and LC MS/MS fractionation sequencing, a novel Bowman Birk-type heptadecapeptide (AALKGCWTKSIPPKPCF-amide), named OSTI, with a canonical Cys6-Cys16 disulfide bridge, was isolated and identified in Piebald Odorous Frog (Odorrana schmackeri) skin secretion. A synthetic replicate of OSTI exhibited trypsin inhibitory activity with a Ki value of 0.3 ± 0.04 nM and also a tryptase inhibitory effect with a Ki of 2.5 ± 0.6 μM. This is the first time that this property has been reported for a peptide originating from amphibian sources. In addition, substituting lysine (K) with phenylalanine (F) at the presumed P1 position, completely abrogated the trypsin and tryptase inhibition, but produced a strong chymotrypsin inhibition with a Ki of 1.0 ± 0.1 μM. Thus, the specificity of this peptidic protease inhibitor could be optimized through modifying the amino acid residue at the presumed P1 position and this novel native OSTI, along with its analogue, [Phe9]-OSTI, have expanded the potential drug discovery and development pipeline directed towards alleviation ofserine protease-mediated pathologies.

KW - Skin secretion. Molecular cloning. Bowman Birk inhibitor. Peptide. Tryptase.

U2 - 10.1042/BSR20160593

DO - 10.1042/BSR20160593

M3 - Article

VL - 37

JO - Bioscience Reports

JF - Bioscience Reports

SN - 0144-8463

IS - 2

ER -