A structural and functional analogue of a Bowman–Birk-type protease inhibitor from <i>Odorrana schmackeri</i>

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

doi:10.1042/bsr20160593

Cited by 16 publications

(25 citation statements)

References 26 publications

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“…The novel peptide B-2Ta was isolated and identified from the skin secretion of Pelophylax kl. esculentus by using “shotgun” cloning with a degenerate sense primer (S1; 5′-GAWYYAYYHRAGCCYAAADATGTTCA-3′) (R=A/G; Y=C/T; H=A/T/C; W=A/T; D=G/A/T) and a NUP primer (supplied with the kit) as described by the manufacturer (Clontech UK) [ 26 ]. LCQ-Fleet™ electrospray ion-trap mass spectrometer was used to confirm the authenticity of the primary structure of the novel peptide from the frog skin secretions [ 26 , 27 ].…”

Section: Methodsmentioning

confidence: 99%

Assessment of antimicrobial and wound healing effects of Brevinin-2Ta against the bacteriumKlebsiella pneumoniaein dermally-wounded rats

Liu

Long

et al. 2017

Oncotarget

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Antimicrobial peptides (AMPs) are regarded as promising alternatives for antibiotics due to their inherent capacity to prevent microbial drug resistance. Amphibians are rich source of bioactive molecules, which provide numerous AMPs with various structures as drug candidates. Here, we isolated and identified a novel AMP Brevinin-2Ta (B-2Ta) from the skin secretion of the European frog, Pelophylax kl. esculentus. In vitro studies revealed that it showed broad antimicrobial activities against S. aureus, E. coli and C. albicans with low cytotoxicity to erythrocytes. Furthermore, we examined the anti-inflammation effect in vivo by using Klebsiella pneumoniae-infected Sprague-Dawley (SD) rats. The wound closure outcomes revealed that B-2Ta effectively restrained the bacterial infection at a dose of 10 times minimal inhibitory concentration (MIC) during the 14 days of the wound healing process. Ultra-structure analyses showed that B-2Ta caused structural damage to the microorganism, and bacterial culture found that the number of microbes was significantly reduced by the end of treatment. Immunohistochemistry for the inflammatory marker IL-10 and the endothelial cell marker CD31 suggested positive effects on inflammatory status and epithelial migration and angiogenesis following treatment of the infected granulation tissues with B-2Ta. These results exhibited the continuous phase of inflammation reduction and wound healing acceleration in the B-2Ta-modulated re-epithelialisation of K. pneumoniae infected rats. Taken together, these data demonstrated that B-2Ta has great potential to be developed as antibacterial agents in clinic.

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Section: Methodsmentioning

confidence: 99%

Assessment of antimicrobial and wound healing effects of Brevinin-2Ta against the bacteriumKlebsiella pneumoniaein dermally-wounded rats

Liu

Long

et al. 2017

Oncotarget

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“…Specimens of P. sauvagei (n = 3, two males 5 cm snout‐to‐vent length, one female 7 cm snout‐to‐vent length), originally from South America, were obtained from a commercial source in the United States. The skin secretion produced by the holocrine glands of frogs was obtained by mild transdermal electrical stimulation (5 V, 50 Hz, 4 ms plus width) as previously described . Secretions were then collected by rinsing with distilled deionized water and were subjected to snap frozen with liquid nitrogen, lyophilized and stored at −20°C prior to use.…”

Section: Methodsmentioning

confidence: 99%

“…The skin secretion produced by the holocrine glands of frogs was obtained by mild transdermal electrical stimulation (5 V, 50 Hz, 4 ms plus width) as previously described. 14…”

Section: Specimen Biodata and Skin Secretion Harvestingmentioning

confidence: 99%

Novel peptide dermaseptin‐PS1 exhibits anticancer activity via induction of intrinsic apoptosis signalling

Long

Wang

et al. 2018

J Cellular Molecular Medi

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Antimicrobial peptides (AMP) secreted by the granular glands of frog skin have been widely reported to exhibit strong bacteriostatic and bactericidal activities. Many of them have been documented with potent antiproliferative effects on multiple cancer cells, many studies also suggested that AMPs exert their functions via disrupting cell membranes. However, whether and how other cell death induction mechanism is involved in mammalian cancer cells has rarely been investigated. In this study, a novel AMP named Dermaseptin‐PS1 was isolated and identified from Phyllomedusa sauvagei, it showed strong antimicrobial activities against three types of microorganisms. In vitro antiproliferative studies on human glioblastoma U‐251 MG cells indicated that Dermaseptin‐PS1 disrupted cell membranes at the concentrations of 10−5 M and above, while the cell membrane integrity was not affected when concentrations were decreased to 10−6 M or lower. Further examinations revealed that, at the relatively low concentration (10−6 M), Dermaseptin‐PS1 induced apoptosis through mitochondrial‐related signal pathway in U‐251 MG cells. Thus, for the first time, we report a novel frog skin derived AMP with anticancer property by distinct mechanisms, which largely depends on its concentration. Together, our study provides new insights into the mechanism‐illustrated drug design and the optimisation of dose control for cancer treatment in clinic.

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“…For 3′-RACE reaction, a nested universal primer (NUP) (supplied with the kit) and a degenerate sense primer were designed and performed as previously reported [ 9 , 10 ]. The 3′-RACE reactions were performed as per previous description [ 11 ].…”

Section: Methodsmentioning

confidence: 99%

The synergistic antimicrobial effects of novel bombinin and bombinin H peptides from the skin secretion of Bombina orientalis

Xiang

Chen

et al. 2017

Bioscience Reports

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Bombinin and bombinin H are two antimicrobial peptide (AMP) families initially discovered from the skin secretion of Bombina that share the same biosynthetic precursor-encoding cDNAs, but have different structures and physicochemical properties. Insight into their possible existing relationship lead us to perform the combination investigations into their anti-infectious activities. In this work, we report the molecular cloning and functional characterization of two novel AMPs belonging to bombinin and bombinin H families from secretions of Bombina orientalis. Their mature peptides (BHL-bombinin and bombinin HL), coded by single ORF, were chemically synthesized along with an analogue peptide that replaced L-leucine with D-leucine from the second position of the N-terminus (bombinin HD). CD analysis revealed that all of them displayed well-defined α-helical structures in membrane mimicking environments. Furthermore, BHL-bombinin displayed broad-spectrum bactericidal activities on a wide range of microorganisms, while bombinin H only exhibited a mildly bacteriostatic effect on the Gram-positive bacteria Staphylococcus aureus. The combination potency of BHL-bombinin with either bombinin HL or bombinin HD showed the synergistic inhibition activities against S. aureus (fractional inhibitory concentration index (FICI): 0.375). A synergistic effect has also been observed between bombinin H and ampicillin, which was further systematically evaluated and confirmed by in vitro time-killing investigations. Haemolytic and cytotoxic examinations exhibited a highly synergistic selectivity and low cytotoxicity on mammalian cells of these three peptides. Taken together, the discovery of the potent synergistic effect of AMPs in a single biosynthetic precursor with superior functional selectivity provides a promising strategy to combat multidrug-resistant pathogens in clinical therapy.

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

Cited by 16 publications

References 26 publications

Assessment of antimicrobial and wound healing effects of Brevinin-2Ta against the bacteriumKlebsiella pneumoniaein dermally-wounded rats

Assessment of antimicrobial and wound healing effects of Brevinin-2Ta against the bacteriumKlebsiella pneumoniaein dermally-wounded rats

Novel peptide dermaseptin‐PS1 exhibits anticancer activity via induction of intrinsic apoptosis signalling

The synergistic antimicrobial effects of novel bombinin and bombinin H peptides from the skin secretion of Bombina orientalis

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