Matches in SemOpenAlex for { <https://semopenalex.org/work/W2980334105> ?p ?o ?g. }
Showing items 1 to 95 of
95
with 100 items per page.
- W2980334105 abstract "Extracellular calcium flow through neuronal voltage-gated Ca V 2.2 calcium channels converts action potential-encoded information to the release of pronociceptive neurotransmitters in the dorsal horn of the spinal cord, culminating in excitation of the postsynaptic central nociceptive neurons. The Ca V 2.2 channel is composed of a pore-forming α 1 subunit (Ca V α 1 ) that is engaged in protein–protein interactions with auxiliary α 2 /δ and β subunits. The high-affinity Ca V 2.2α 1 ⋅Ca V β 3 protein–protein interaction is essential for proper trafficking of Ca V 2.2 channels to the plasma membrane. Here, structure-based computational screening led to small molecules that disrupt the Ca V 2.2α 1 ⋅Ca V β 3 protein–protein interaction. The binding mode of these compounds reveals that three substituents closely mimic the side chains of hot-spot residues located on the α-helix of Ca V 2.2α 1 . Site-directed mutagenesis confirmed the critical nature of a salt-bridge interaction between the compounds and Ca V β 3 Arg-307. In cells, compounds decreased trafficking of Ca V 2.2 channels to the plasma membrane and modulated the functions of the channel. In a rodent neuropathic pain model, the compounds suppressed pain responses. Small-molecule α-helical mimetics targeting ion channel protein–protein interactions may represent a strategy for developing nonopioid analgesia and for treatment of other neurological disorders associated with calcium-channel trafficking." @default.
- W2980334105 created "2019-10-25" @default.
- W2980334105 creator A5009770607 @default.
- W2980334105 creator A5022469850 @default.
- W2980334105 creator A5028048039 @default.
- W2980334105 creator A5036387210 @default.
- W2980334105 creator A5039309910 @default.
- W2980334105 creator A5040100986 @default.
- W2980334105 creator A5040946263 @default.
- W2980334105 creator A5041652292 @default.
- W2980334105 creator A5055133888 @default.
- W2980334105 creator A5060548515 @default.
- W2980334105 creator A5076222076 @default.
- W2980334105 date "2018-11-06" @default.
- W2980334105 modified "2023-09-26" @default.
- W2980334105 title "Small-molecule CaVα1⋅CaVβ antagonist suppresses neuronal voltage-gated calcium-channel trafficking" @default.
- W2980334105 hasPublicationYear "2018" @default.
- W2980334105 type Work @default.
- W2980334105 sameAs 2980334105 @default.
- W2980334105 citedByCount "0" @default.
- W2980334105 crossrefType "journal-article" @default.
- W2980334105 hasAuthorship W2980334105A5009770607 @default.
- W2980334105 hasAuthorship W2980334105A5022469850 @default.
- W2980334105 hasAuthorship W2980334105A5028048039 @default.
- W2980334105 hasAuthorship W2980334105A5036387210 @default.
- W2980334105 hasAuthorship W2980334105A5039309910 @default.
- W2980334105 hasAuthorship W2980334105A5040100986 @default.
- W2980334105 hasAuthorship W2980334105A5040946263 @default.
- W2980334105 hasAuthorship W2980334105A5041652292 @default.
- W2980334105 hasAuthorship W2980334105A5055133888 @default.
- W2980334105 hasAuthorship W2980334105A5060548515 @default.
- W2980334105 hasAuthorship W2980334105A5076222076 @default.
- W2980334105 hasConcept C104292427 @default.
- W2980334105 hasConcept C104317684 @default.
- W2980334105 hasConcept C12554922 @default.
- W2980334105 hasConcept C170493617 @default.
- W2980334105 hasConcept C178790620 @default.
- W2980334105 hasConcept C185592680 @default.
- W2980334105 hasConcept C18699975 @default.
- W2980334105 hasConcept C197341189 @default.
- W2980334105 hasConcept C28406088 @default.
- W2980334105 hasConcept C30979828 @default.
- W2980334105 hasConcept C37088560 @default.
- W2980334105 hasConcept C50254741 @default.
- W2980334105 hasConcept C519063684 @default.
- W2980334105 hasConcept C55493867 @default.
- W2980334105 hasConcept C85520022 @default.
- W2980334105 hasConcept C86803240 @default.
- W2980334105 hasConcept C92645518 @default.
- W2980334105 hasConcept C95444343 @default.
- W2980334105 hasConceptScore W2980334105C104292427 @default.
- W2980334105 hasConceptScore W2980334105C104317684 @default.
- W2980334105 hasConceptScore W2980334105C12554922 @default.
- W2980334105 hasConceptScore W2980334105C170493617 @default.
- W2980334105 hasConceptScore W2980334105C178790620 @default.
- W2980334105 hasConceptScore W2980334105C185592680 @default.
- W2980334105 hasConceptScore W2980334105C18699975 @default.
- W2980334105 hasConceptScore W2980334105C197341189 @default.
- W2980334105 hasConceptScore W2980334105C28406088 @default.
- W2980334105 hasConceptScore W2980334105C30979828 @default.
- W2980334105 hasConceptScore W2980334105C37088560 @default.
- W2980334105 hasConceptScore W2980334105C50254741 @default.
- W2980334105 hasConceptScore W2980334105C519063684 @default.
- W2980334105 hasConceptScore W2980334105C55493867 @default.
- W2980334105 hasConceptScore W2980334105C85520022 @default.
- W2980334105 hasConceptScore W2980334105C86803240 @default.
- W2980334105 hasConceptScore W2980334105C92645518 @default.
- W2980334105 hasConceptScore W2980334105C95444343 @default.
- W2980334105 hasLocation W29803341051 @default.
- W2980334105 hasOpenAccess W2980334105 @default.
- W2980334105 hasPrimaryLocation W29803341051 @default.
- W2980334105 hasRelatedWork W1535117441 @default.
- W2980334105 hasRelatedWork W1641738400 @default.
- W2980334105 hasRelatedWork W1998239075 @default.
- W2980334105 hasRelatedWork W2025150024 @default.
- W2980334105 hasRelatedWork W2040766257 @default.
- W2980334105 hasRelatedWork W2042771144 @default.
- W2980334105 hasRelatedWork W2051502084 @default.
- W2980334105 hasRelatedWork W2057198039 @default.
- W2980334105 hasRelatedWork W2057344543 @default.
- W2980334105 hasRelatedWork W2065040835 @default.
- W2980334105 hasRelatedWork W2066246595 @default.
- W2980334105 hasRelatedWork W2124030990 @default.
- W2980334105 hasRelatedWork W2127079625 @default.
- W2980334105 hasRelatedWork W2159998111 @default.
- W2980334105 hasRelatedWork W2160827670 @default.
- W2980334105 hasRelatedWork W2167441016 @default.
- W2980334105 hasRelatedWork W2260657277 @default.
- W2980334105 hasRelatedWork W2898602871 @default.
- W2980334105 hasRelatedWork W2977658353 @default.
- W2980334105 hasRelatedWork W3082053037 @default.
- W2980334105 isParatext "false" @default.
- W2980334105 isRetracted "false" @default.
- W2980334105 magId "2980334105" @default.
- W2980334105 workType "article" @default.