Inhibitory and antimicrobial activities of OGTI and HV-BBI peptides, fragments and analogs derived from amphibian skin

Dębowski, Dawid; Łukajtis, Rafał; Łęgowska, Anna; Karna, Natalia; Pikuła, Michał; Wysocka, Magdalena; Maliszewska, Irena; Sieńczyk, Marcin; Lesner, Adam; Rolka, Krzysztof

doi:10.1016/j.peptides.2012.04.001

Cited by 19 publications

(32 citation statements)

References 38 publications

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“…The molar concentration of each peptide was determined using HPLC method as described previously [19]. Peptides were dissolved in 50 m m Tris-HCl (pH 8.1) buffer at concentration of about 4 mg/m l .…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Human and Yeast 20S Proteasome by Analogues of Trypsin Inhibitor SFTI-1

et al. 2014

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Starting from the primary structure of sunflower trypsin inhibitor SFTI-1, we designed novel non-covalent inhibitors of human and yeast 20S proteasomes. Peptides with Arg residue in P1 position and two basic amino acid residues (Lys or/and Arg) in P2′ and P3′ positions strongly inhibited chymotrypsin-like and caspase-like activities, while trypsin-like activity was poorly modified. We found that some SFTI-1 analogues up-regulated exclusively the chymotrypsin-like activity of latent yeast 20S proteasome.

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Section: Methodsmentioning

confidence: 99%

Inhibition of Human and Yeast 20S Proteasome by Analogues of Trypsin Inhibitor SFTI-1

et al. 2014

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“…However, from the different activities of the medusins against Gram-positive and Gram-negative bacteria, it is clear that differences in the structures of outer membranes can induce differential susceptibilities (Dȩbowski et al, 2012). In particular, the outer membrane of Gram-negative bacteria could trap the AMPs to prevent their further translocation thereby protecting the cytoplasmic membrane.…”

Section: Discussionmentioning

confidence: 99%

Targeted Modification of a Novel Amphibian Antimicrobial Peptide from Phyllomedusa tarsius to Enhance Its Activity against MRSA and Microbial Biofilm

Gao

Wang

et al. 2017

Front. Microbiol.

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Antimicrobial peptides (AMPs) in the skin secretions of amphibians are fundamental components of a unique defense system that has evolved to protect these hosts from microbial invasion. Medusins constitute a recently-discovered AMP family from phyllomedusine leaf frog skin and exhibit highly-conserved structural characteristics. Here, we report a novel medusin, medusin-PT, from the skin secretion of the Tarsier Leaf Frog, Phyllomedusa tarsius. The mature peptide was initially identified from its cloned biosynthetic precursor-encoding cDNA as obtained by the rapid amplification of cDNA ends (RACE) method. Reverse-phase HPLC and tandem mass spectrometry confirmed both the presence of medusin-PT in the skin secretion and its primary structure. In a range of bioassays, medusin-PT exhibited antimicrobial activity against only the Gram-positive bacterium Staphylococcus aureus at 64 μg/ml. However, after directed changes to enhance the cationicity and amphipathicity of the peptide structure, three analog showed more potent antimicrobial activity against several additional bacteria including the antibiotic-resistant bacterium MRSA. In addition, these analog exhibited activity against microbial biofilm (minimum biofilm inhibitory and eradication concentrations of 32 μg/ml and over 64 μg/ml, respectively). These data provide evidence that medusins might be promising candidates as novel antibiotic leads and that the targeted modification of a natural AMP can both improve its efficacy so as to provide new insights into antibiotic design and development.

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“…The HV‐BBI(3‐18) peptide was synthesized as previously described by Debowski et al . Bovine pancreatic trypsin was obtained from BioShop (Canada).…”

Section: Methodsmentioning

confidence: 99%

“…We (as well as others) have recently demonstrated that certain inhibitors derived from amphibian skin secretions have a dual role possessing both antimicrobial and protease inhibitory activities . Since such compounds can be regarded as promising candidates for novel antibiotics, the further characterization of their properties is most interesting.…”

Section: Introductionmentioning

confidence: 99%

Atomic resolution crystal structure of HV-BBI protease inhibitor from amphibian skin in complex with bovine trypsin

et al. 2015

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Protease inhibitors of the Bowman-Birk (BBI) family are commonly found in plants and animals where they play a protective role against invading pathogens. Here, we report an atomic resolution (1Å) crystal structure of a peptide inhibitor isolated from a skin secretion of a Chinese bamboo odorous frog Huia versabilis (HV-BBI) in complex with trypsin. HV-BBI shares significant similarities in sequence with a previously described inhibitor from a diskless-fingered odorous frog Odorrana graham (ORB). However, the latter is characterized by more than a 16,000 fold higher Ki against trypsin than HV-BBI. Comparative analysis of trypsin cocrystal structures of HV-BBI and ORB and additionally that of Sunflower Trypsin Inhibitor (SFTI-1) together with accessory information on the affinities of inhibitor variants allowed us to pinpoint the inhibitor moiety responsible for the observed large difference in activity and also to define the extent of modifications permissible within the common protease-binding loop scaffold of BBI inhibitors. We suggest that modifications outside of the inhibitory loop permit the evolution of specificity toward different enzymes characterized by trypsin-like specificity.

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Inhibitory and antimicrobial activities of OGTI and HV-BBI peptides, fragments and analogs derived from amphibian skin

Cited by 19 publications

References 38 publications

Inhibition of Human and Yeast 20S Proteasome by Analogues of Trypsin Inhibitor SFTI-1

Inhibition of Human and Yeast 20S Proteasome by Analogues of Trypsin Inhibitor SFTI-1

Targeted Modification of a Novel Amphibian Antimicrobial Peptide from Phyllomedusa tarsius to Enhance Its Activity against MRSA and Microbial Biofilm

Atomic resolution crystal structure of HV-BBI protease inhibitor from amphibian skin in complex with bovine trypsin

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