scholarly journals Kunitzins: Prototypes of a new class of protease inhibitor from the skin secretions of European and Asian frogs

2016 ◽  
Vol 477 (2) ◽  
pp. 302-309 ◽  
Author(s):  
Xiaole Chen ◽  
He Wang ◽  
Yue Shen ◽  
Lei Wang ◽  
Mei Zhou ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
New Class ◽  
Skin Secretions

scholarly journals Discovery and Rational Design of a Novel Bowman-Birk Related Protease Inhibitor

Biomolecules ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 280 ◽  
Author(s):  
Yuxi Miao ◽  
Guanzhu Chen ◽  
Xinping Xi ◽  
Chengbang Ma ◽  
Lei Wang ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Inhibitory Activity ◽  
Rational Design ◽  
Cdna Sequence ◽  
Cell Penetrating Peptide ◽  
Skin Secretion ◽  
Amphibian Skin ◽  
Skin Secretions ◽  
Inhibitor Drug ◽  
Potent Inhibitory Activity

Anuran amphibian skin secretions are a rich source of peptides, many of which represent novel protease inhibitors and can potentially act as a source for protease inhibitor drug discovery. In this study, a novel bioactive Bowman-Birk type inhibitory hexadecapeptide of the Ranacyclin family from the defensive skin secretion of the Fukien gold-striped pond frog, Pelophlax plancyi fukienesis, was successfully isolated and identified, named PPF-BBI. The primary structure of the biosynthetic precursor was deduced from a cDNA sequence cloned from a skin-derived cDNA library, which contains a consensus motif representative of the Bowman-Birk type inhibitor. The peptide was chemically synthesized and displayed a potent inhibitory activity against trypsin (Ki of 0.17 µM), as well as an inhibitory activity against tryptase (Ki of 30.73 µM). A number of analogues of this peptide were produced by rational design. An analogue, which substituted the lysine (K) at the predicted P1 position with phenylalanine (F), exhibited a potent chymotrypsin inhibitory activity (Ki of 0.851 µM). Alternatively, a more potent protease inhibitory activity, as well as antimicrobial activity, was observed when P16 was replaced by lysine, forming K16-PPF-BBI. The addition of the cell-penetrating peptide Tat with a trypsin inhibitory loop resulted in a peptide with a selective inhibitory activity toward trypsin, as well as a strong antifungal activity. This peptide also inhibited the growth of two lung cancer cells, H460 and H157, demonstrating that the targeted modifications of this peptide could effectively and efficiently alter its bioactivity.

Cysteine Protease Inhibitor from Pearl Millet: A New Class of Antifungal Protein

1998 ◽  
Vol 246 (2) ◽  
pp. 382-387 ◽  
Author(s):  
Bimba N. Joshi ◽  
Mohini N. Sainani ◽  
Kulbhushan B. Bastawade ◽  
Vidya S. Gupta ◽  
Prabhakar K. Ranjekar
Keyword(s):  
Protease Inhibitor ◽  
Pearl Millet ◽  
Cysteine Protease ◽  
Cysteine Protease Inhibitor ◽  
Antifungal Protein ◽  
New Class

scholarly journals A structural and functional analogue of a Bowman–Birk-type protease inhibitor from Odorrana schmackeri

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Yuxin Wu ◽  
Qilin Long ◽  
Ying Xu ◽  
Shaodong Guo ◽  
Tianbao Chen ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Frog Skin ◽  
Disulfide Bridge ◽  
Inhibitory Effect ◽  
Skin Secretion ◽  
Drug Discovery And Development ◽  
Trypsin Inhibitory Activity ◽  
Skin Secretions ◽  
Development Pipeline ◽  
First Time

Frog skin secretions contain complex peptidomes and peptidic protease inhibitors that are one of the biologically and structurally described groups of components. In the present study, by use of molecular ‘shotgun’ cloning and LC MS/MS fractionation sequencing, a novel Bowman–Birk-type heptadecapeptide (AALKGCWTKSIPPKPCF-amide), named Odorrana schmackeriTrypsin Inhibitor (OSTI), with a canonical Cys6–Cys16 disulfide bridge, was isolated and identified in piebald odorous frog (O. 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.

A new class of HIV-1 protease inhibitor: The crystallographic structure, inhibition and chemical synthesis of an aminimide peptide isostere

1996 ◽  
Vol 4 (9) ◽  
pp. 1545-1558 ◽  
Author(s):  
Earl E. Rutenber ◽  
Fiona McPhee ◽  
Alan P. Kaplan ◽  
Steven L. Gallion ◽  
Joseph C. Hogan ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Protease Inhibitor ◽  
Crystallographic Structure ◽  
New Class ◽  
Hiv 1

Medusins: A new class of antimicrobial peptides from the skin secretions of phyllomedusine frogs

Biochimie ◽  
2013 ◽  
Vol 95 (6) ◽  
pp. 1288-1296 ◽  
Author(s):  
Xinping Xi ◽  
Renjie Li ◽  
Yingchun Jiang ◽  
Yan Lin ◽  
Yuxin Wu ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
New Class ◽  
Skin Secretions
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