Bioactive peptides from Rana (Odorrana) frog secretions

• Main Author: Wu, Yuxin
• Published: Queen's University Belfast 2013
• Subjects: 597.89
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603569

The studies described in this thesis have focused on the bioactive peptides secreted from the skin glands of Rana (Odorrana) frogs, using different techniques to identify the sequences of novel peptides and to subsequently clone their precursors by molecular genetic techniques and finally, to chemically-synthesize these peptides and examine their bioactivities. Chapters I and 2, respectively, give a general introduction to the field of research and describe the scientific techniques employed in the work. The first experimental chapter, Chapter 3, describes two novel non-canonical bradykinin antagonist peptides isolated from the skin secretion of Odorrana versabilis which contain a "Rana box"-like structure at their C-terminals- a motif that is normally present in antimicrobial peptides. Chapter 4 describes a novel tachykinin peptide which was isolated from the skin of Rana chensinensis, and is strongly suspected of being an NKI receptor agonist. Chapter 5 describes the identification of two novel peptides from the skin secretions of Odorrana versabifis and Odorrana livida, which possess a moderate degree of specific antifungal activity. How their similar primary structures with only two residue substitutions, can cause an apparent 4-fold difference in potency is an interesting observation worthy of further indepth study. Chapter 6 describes a study that focuses on a Bowman-Birk trypsin inhibitor peptide from Odorrana schmackeri skin secretion and its position 9 substituted analogue. The most interesting result was the discovery of their multi-functional effects, not only against the proteases, trypsin and chymotrypsin, but also extending to growth inhibitory effects on cancer cell lines, tryptase inhibition and even to smooth muscle effects. The structure/function relationships of these peptides require further in-depth investigations. Chapter 7 describes a novel vasodilator peptide, named vasorelaxin, isolated from Odorrana schmackeri skin secretion with a potency approaching two orders of magnitude greater than canonical bradykinin. These data further illustrate that Rana (Odorrana) frogs skin secretions remain an important resource for novel peptide discovery, some of which may possess therapeutic properties.