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Solution structure of antifungal plant defensin PvD1
Structural highlights
Publication Abstract from PubMedAvailable treatments of invasive fungal infection have limitations including toxicity and the emergence of resistant strains. Therefore, there is an urgent need for alternative solutions. Due to the unique mode of action and high selectivity, plant defensins (PDs) are worthy therapeutic candidates. Chemical synthesis remains a preferred method for the production of many peptide-based therapeutics. Given the relatively long sequence of PDs, as well as their complicated posttranslational modifications, the synthetic route can be considered challenging. Here we describe a total synthesis of PvD1, the defensin from the common bean Phaseolus vulgaris. Analytical, structural and functional characterization revealed that both natural and synthetic peptides fold into a canonical CSalphabeta motif stabilized by conserved disulfide bonds. Moreover, synthetic PvD1 retained the biological activity against four different Candida species and showed no toxicity in-vivo. Adding the high resistance of synthetic PvD1 to proteolytic degradation we claim that conditions are now met to consider plant defensins druggable biologicals. Synthesis, structure, and activity of the antifungal plant defensin PvD1.,Skalska J, Andrade VM, Cena GL, Harvey PJ, Gaspar DMD, Mello EO, Troeira Henriques S, Valle J, Gomes V, Conceicao K, Castanho MARB, Andreu D J Med Chem. 2020 Aug 6. doi: 10.1021/acs.jmedchem.0c00543. PMID:32787086[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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