Design, synthesis and biological evaluation of two opioid agonist and Cav2.2 blocker multitarget ligands

Mollica, Adriano, Costante, Roberto, Novellino, Ettore, Stefanucci, Azzurra, Pieretti, Stefano, Zador, Ferenc, Samavati, Reza, Borsodi, Anna, Benyhe, Sandor, Vetter, Irina and Lewis, Richard J. (2014) Design, synthesis and biological evaluation of two opioid agonist and Cav2.2 blocker multitarget ligands. Chemical Biology and Drug Design, 86 2: 156-162. doi:10.1111/cbdd.12479


Author Mollica, Adriano
Costante, Roberto
Novellino, Ettore
Stefanucci, Azzurra
Pieretti, Stefano
Zador, Ferenc
Samavati, Reza
Borsodi, Anna
Benyhe, Sandor
Vetter, Irina
Lewis, Richard J.
Title Design, synthesis and biological evaluation of two opioid agonist and Cav2.2 blocker multitarget ligands
Journal name Chemical Biology and Drug Design   Check publisher's open access policy
ISSN 1747-0277
1747-0285
Publication date 2014-12-08
Year available 2014
Sub-type Article (original research)
DOI 10.1111/cbdd.12479
Volume 86
Issue 2
Start page 156
End page 162
Total pages 7
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell
Collection year 2015
Language eng
Formatted abstract
N-type voltage-dependent Ca2+ channels (CaV2.2) are located at nerve endings in the central and peripheral nervous systems and are strongly associated with the pathological processes of cerebral ischaemia and neuropathic pain. CaV2.2 blockers such as the ω-conotoxin MVIIA (Prialt) are analgesic and have opioid-sparing effects. With the aim to develop new multitarget analgesic compounds, we designed the first ω-conotoxin/opioid peptidomimetics based on the enkephalin-like sequence Tyr-D-Ala-Gly-Phe (for the opioid portion) and two fragments derived from the loop-2 pharmacophore of ω-conotoxin MVIIA. Antinociceptive activity evaluated in vitro and in vivo revealed differential affinity for CaV2.2 and opioid receptors and no significant synergistic activity
Keyword Analgesic
CaV2.2
Conotoxin
Multitarget ligands
Opioid
Pain
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 8 December 2014.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 06 Jan 2015, 00:49:46 EST by Susan Allen on behalf of Institute for Molecular Bioscience