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Your search keyword '"Fergus, S."' showing total 4 results
Start Over Author "Fergus, S." Journal peptide science
4 results on '"Fergus, S."'

1. <scp>μ‐Conotoxin KIIIA</scp> peptidomimetics that block human <scp>voltage‐gated</scp> sodium channels

Author

Rachel Whiting, Brian O. Smith, Christopher M. Timperley, A. Christopher Green, Astrid Knuhtsen, Fergus S. McWhinnie, Kenneth I. Kinnear, Charlotte Whitmore, and Andrew G. Jamieson

Subjects
Biomaterials, 010405 organic chemistry, Peptidomimetic, Chemistry, Sodium channel, Organic Chemistry, Biophysics, 010402 general chemistry, 01 natural sciences, Biochemistry, μ conotoxin, 0104 chemical sciences
Abstract

Peptidomimetics designed to target voltage‐gated sodium channels have attracted significant attention as potential analgesics. However, voltage‐gated sodium channel (VGSC)‐blocking activity of these compounds has mainly been assessed using rat and/or mice homologs. In this study, we developed a novel series of conformationally constrained peptidomimetic analogues of the μ‐conotoxin KIIIA and assessed their activity against human VGSCs. Two of the mimetics block the currents of hNav1.4 and hNav1.6 channels. NMR derived structures of the mimetics provided excellent insight into the structural requirements for bioactivity. A lactam‐constrained analogue, previously reported to be active in mice, did not block the corresponding human VGSC. This work highlights important differences in VGSCs between species and validates the potential of peptidomimetics as human analgesics.

Published
2020

3. μ‐Conotoxin KIIIA peptidomimetics that block human voltage‐gated sodium channels.

Author

Knuhtsen, Astrid, Whiting, Rachel, McWhinnie, Fergus S., Whitmore, Charlotte, Smith, Brian O., Green, A. Christopher, Timperley, Christopher M., Kinnear, Kenneth I., and Jamieson, Andrew G.

Subjects
PEPTIDOMIMETICS, PYRETHROIDS, SODIUM channels, ANALGESICS, HUMAN beings
Abstract

Peptidomimetics designed to target voltage‐gated sodium channels have attracted significant attention as potential analgesics. However, voltage‐gated sodium channel (VGSC)‐blocking activity of these compounds has mainly been assessed using rat and/or mice homologs. In this study, we developed a novel series of conformationally constrained peptidomimetic analogues of the μ‐conotoxin KIIIA and assessed their activity against human VGSCs. Two of the mimetics block the currents of hNav1.4 and hNav1.6 channels. NMR derived structures of the mimetics provided excellent insight into the structural requirements for bioactivity. A lactam‐constrained analogue, previously reported to be active in mice, did not block the corresponding human VGSC. This work highlights important differences in VGSCs between species and validates the potential of peptidomimetics as human analgesics. [ABSTRACT FROM AUTHOR]

Published
2021
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4. μ‐Conotoxin KIIIApeptidomimetics that block human voltage‐gatedsodium channels

Author

Knuhtsen, Astrid, Whiting, Rachel, McWhinnie, Fergus S., Whitmore, Charlotte, Smith, Brian O., Green, A. Christopher, Timperley, Christopher M., Kinnear, Kenneth I., and Jamieson, Andrew G.

Abstract

Peptidomimetics designed to target voltage‐gated sodium channels have attracted significant attention as potential analgesics. However, voltage‐gated sodium channel (VGSC)‐blocking activity of these compounds has mainly been assessed using rat and/or mice homologs. In this study, we developed a novel series of conformationally constrained peptidomimetic analogues of the μ‐conotoxin KIIIA and assessed their activity against human VGSCs. Two of the mimetics block the currents of hNav1.4 and hNav1.6 channels. NMR derived structures of the mimetics provided excellent insight into the structural requirements for bioactivity. A lactam‐constrained analogue, previously reported to be active in mice, did not block the corresponding human VGSC. This work highlights important differences in VGSCs between species and validates the potential of peptidomimetics as human analgesics.

Published
2021
Full Text
View/download PDF

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