Exploring the Pharmacological Potential of Bioactive Peptides in Amphibians and Plants: from Identification to Rational Design
Bioactive peptides, which can be seen as a part of the innate immune response in most living things, are derived from bacteria, fungi, amphibians, insects, mammals, plants and many other sources. Here, Dermaseptin-PC (DM-PC) and PLX-PC, two novel AMPs (antimicrobial peptides), were discovered from the skin secretion of a tree-dwelling, South American frog (Phyllomedusa coelestis), using the combination of ‘shotgun’ cloning and tandem mass spectrometry fragmentation sequencing. Besides, the successful molecular cloning of a novel trypsin inhibitor (as the probable alleleic variants TKTI-2 and TKTI-3) from the dried root of Trichosanthes kirilowii indicates that mRNA can persist in decoction pieces and so could present a viable option for the molecular cloning from other TCMs. It is noteworthy that host-defence peptides have evolved as highly potent alternatives to antibiotics, exerting powerful physiological effects and high susceptibility of multidrug-resistant strains. However, some intrinsic weaknesses limit the direct usage of naturally occurring peptides as convenient therapeutics. Consequently, DM-PC was rational designed with the objective of a higher therapeutic index, while PLX-PC was further modified by substitution of amino acids and truncating the effective part for higher potency and broader spectrum of antimicrobial activity. With the optimisation of physicochemical characteristics of these two bioactive natural peptides, their bio-efficacy and therapeutic indices were enhanced. The study of these together with their analogues provides new insights on lead antibiotic drug discovery and design, especially against resistant strains. Thesis embargoed until 31st November 2024
Networked Digital Library of Theses and Dissertations