What is it about?
A series of dimeric derivatives of amantadine were generated and tested as ligands of the M2 channel of the influenza virusa and the p7 channel of hepatitis C. Amantadine is a known channel blocker and inhibitor of both channels. Dimers, containing two amantadine molecules linked by a spacer were synthesized and their activity against M2- and p7-channels tested by patch-clamp electrophysiology. Dimeric amantadines showed similar inhibitory activity as monomeric ligands, but their geometry helped to identify key residues for interactio nbetwen the viroporin and the ligand.
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Why is it important?
Dimeric ligands are an intriguing concept to generate more specific inhibitors of disease-related proteins. If two binding sites exist, dimers can indeed be more active than the related monomer. As the spacer length in a dimeric ligand can be varied, these moelcules can also be used to identify the distance between inhibitor binding sites on the protein.
Perspectives
Such studies are important as they combine theoretical analysis and simulation with biochemical data. Potential benefits are (i) generation of more powerful pharmaceuticals, and (ii) a better understanding of protein structure-function relations.
Dr. Hans-Georg Breitinger
German University in Cairo
Read the Original
This page is a summary of: Symmetric dimeric adamantanes for exploring the structure of two viroporins: influenza virus M2 and hepatitis C virus p7, Drug Design Development and Therapy, April 2018, Dove Medical Press,
DOI: 10.2147/dddt.s157104.
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