Melbourne Dental School - Research Publications

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    Integrating Oral and General Health Care in Australia: Utilising Aged Care to demonstrate essential elements of this global issue.
    Martin, R ; Calache, H ; George, A (UBIQUITY PRESS LTD, 2021-01-01)
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    Collaborative Oral Health Care
    Mamerto, ML ; Calache, H ; Ivanovic, A ; Bettega, A ; Martin, RE ; McKee, S (UBIQUITY PRESS LTD, 2021-01-01)
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    C-terminus amidation influences biological activity and membrane interaction of maculatin 1.1
    Zhu, S ; Li, W ; O'Brien-Simpson, N ; Separovic, F ; Sani, M-A (SPRINGER WIEN, 2021-04-23)
    Cationic antimicrobial peptides have been investigated for their potential use in combating infections by targeting the cell membrane of microbes. Their unique chemical structure has been investigated to understand their mode of action and optimize their dose-response by rationale design. One common feature among cationic AMPs is an amidated C-terminus that provides greater stability against in vivo degradation. This chemical modification also likely modulates the interaction with the cell membrane of bacteria yet few studies have been performed comparing the effect of the capping groups. We used maculatin 1.1 (Mac1) to assess the role of the capping groups in modulating the peptide bacterial efficiency, stability and interactions with lipid membranes. Circular dichroism results showed that C-terminus amidation maintains the structural stability of the peptide (α-helix) in contact with micelles. Dye leakage experiments revealed that amidation of the C-terminus resulted in higher membrane disruptive ability while bacteria and cell viability assays revealed that the amidated form displayed higher antibacterial ability and cytotoxicity compared to the acidic form of Mac1. Furthermore, 31P and 2H solid-state NMR showed that C-terminus amidation played a greater role in disturbance of the phospholipid headgroup but had little effect on the lipid tails. This study paves the way to better understand how membrane-active AMPs act in live bacteria.