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Title: Biological effects of novel amphibian skin peptides and their catabolism
Author: Wang, Ran
ISNI:       0000 0004 2726 4030
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2012
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Amphibian skin secretions are known to contain numerous peptides with a large array of biological activities. Among the anuran amphibians, the Neotropical hylid frogs belonging to the subfamily Phyllomedusinae, are an excellent source of such bioactive peptides with antimicrobial and pharmacological activities. To date, more than 200 peptides from this frog taxon have been reported in the scientific literature and their structures have been deposited in genomic and proteomic data banks such as the Universal Protein Resource Consortium (UniProt). In this thesis, we have identified four novel tryptophyllins (TPHs) from the skin secretions of four different phyllomedusine species (Phyllomedusa sauvagei, Phyllomedusa hypocondrialis, Agalyehnis eallidryas and Phyllomedusa bieolor). The primary structures of these peptides were determined by combinations of Edman degradation and mass spectrometry techniques. Molecular cloning of respective cDNA sequences encoding the precursors of these TPHs was achieved from skin cDNA libraries of each species. The amino acid sequences deduced from the nucleotide sequences of cloned precursor cDNAs corresponded exactly with those obtained by chemical/mass spectrometric techniques. Some of these novel TPH peptides were found to have potent effects on mammalian smooth muscle and here we report for the first time that TPHs can antagonise the bradykinin-induced relaxation responses in rat tail artery smooth muscle preparations and that they have anticancer effects on human prostate cancer (LNCaPIPC3IDU145) cell lines. The catabolism of these TPHs by prostate cancer cells was analysed and all were found to be highly-resistant to degradation under the experimental conditions employed. The polyadenylated mRNAs encoding both bradykinin receptor subtypes, Bland B2, were also shown to be expressed in all three prostate cancer cell lines through molecular cloning of specific receptor cDNA fragments from cDNA libraries constructed from each. These data suggest that bradykinin receptors could be a hitherto uninvestigated target of potential utility in the treatment of prostate cancer. The data generated through the discrete studies reported in this thesis may aid in the understanding of possible biological roles played by amphibian skin TPHs and the contributions made by specific structural features within this heterogenous and largely unstudied family of amphibian skin peptides. The peptides described here for the first time may represent novel lead compounds for the design/development of new therapeutics for human neoplastic disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available