RgIA [S4T,R9(Cit),Y10(Ity),R11Q,R13Y] (P08507) Protein Card

General Information
Name RgIA [S4T,R9(Cit),Y10(Ity),R11Q,R13Y] (named by ConoServer)
Alternative name(s) RgIA4
Organism synthetic construct
Protein Type Synthetic
Parent RgIA
Notes Huynh et al. 2019 reported that treatment of Sprague Dawley rats with RgIA4 (80 μg/kg) showed significant recovery from mechanical allodynia by day 31.

Classification
Conopeptide class conotoxin
Gene superfamily
Pharmacological family alpha conotoxin

Sequence
GCCTDPRC(Cit)(Ity)QCY
Modified residues
positionsymbolname
9CitCitrulline
10Ity3-iodotyrosine
Average Mass 1690.63
Monoisotopic Mass 1689.43
Isoelectric Point 8.09
Extinction Coefficient [280nm] 1490.00

Activity

IC50: Nicotinic acetylcholine receptors

TargetOrganismIC50nhillAgonistRef
α1β1δεH. sapiens>10 uM10 uM AChRomero,H.K. et al. (2017)
R. norvegicus>10 uM10 uM AChRomero,H.K. et al. (2017)
α2β2H. sapiens>10 uM10 uM AChRomero,H.K. et al. (2017)
R. norvegicus>10 uM10 uM AChRomero,H.K. et al. (2017)
α2β4H. sapiens>10 uM10 uM AChRomero,H.K. et al. (2017)
R. norvegicus>10 uM10 uM AChRomero,H.K. et al. (2017)
α3β2H. sapiens>10 uM10 uM AChRomero,H.K. et al. (2017)
R. norvegicus>10 uM10 uM AChRomero,H.K. et al. (2017)
α3β4H. sapiens>10 uM10 uM AChRomero,H.K. et al. (2017)
R. norvegicus>10 uM10 uM AChRomero,H.K. et al. (2017)
α4β2H. sapiens>10 uM10 uM AChRomero,H.K. et al. (2017)
R. norvegicus>10 uM10 uM AChRomero,H.K. et al. (2017)
α4β4H. sapiens>10 uM10 uM AChRomero,H.K. et al. (2017)
>10 uM10 uM AChRomero,H.K. et al. (2017)
R. norvegicus>10 uM10 uM AChRomero,H.K. et al. (2017)
α7H. sapiens1.8 uM10 uM AChRomero,H.K. et al. (2017)
M. musculus4.5 uM[3.1-6.4]2Christensen et al. (2017)
R. norvegicus>10 uM10 uM AChRomero,H.K. et al. (2017)
α9α10H. sapiens1.5 nM+/-0.51.1410 uM AChRomero,H.K. et al. (2017)
1.5 nM[0.5-2.5]100 uM AChZheng N et al. (2021)
M. musculus1.2 nM[0.95-1.6]1.6Christensen et al. (2017)
R. norvegicus0.9 nM+/-0.60.8210 uM AChRomero,H.K. et al. (2017)
0.9 nM+/-0.60.8210 uM AChRomero,H.K. et al. (2017)

Percentage inhibition: Nicotinic acetylcholine receptors

TargetOrganism% inhibitionConcentrationRef
α1β1δεM. musculus95+/-410 uMChristensen et al. (2017)
α1β1γδM. musculus86+/-410 uMChristensen et al. (2017)
α3β2M. musculus106+/-310 uMChristensen et al. (2017)
α3β4M. musculus105+/-110 uMChristensen et al. (2017)
α4β2M. musculus102+/-310 uMChristensen et al. (2017)
α4β4M. musculus74+/-310 uMChristensen et al. (2017)

References
Christensen, S.B., Hone, A.J., Roux, I., Kniazeff, J., Pin, J.P., Upert, G., Servent, D., Glowatzki, E. and McIntosh, J.M. (2017) RgIA4 potently blocks mouse α9α10 nAChRs and provides long lasting protection against oxaliplatin-induced cold allodynia Frontiers in cellular neuroscience 11:219
Huynh,P.N., Giuvelis,D., Christensen,S., Tucker,K.L. and McIntosh,J.M. (2019) RgIA4 Accelerates Recovery from Paclitaxel-Induced Neuropathic Pain in Rats Mar Drugs 18:12
Romero,H.K., Christensen,S.B., Di Cesare Mannelli,L., Gajewiak,J., Ramachandra,R., Elmslie,K.S., Vetter,D.E., Ghelardini,C., Iadonato,S.P., Mercado,J.L., Olivera,B.M. and McIntosh,J.M. (2017) Inhibition of α9α10 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain. Proc Natl Acad Sci U S A 114
Zheng N, Christensen SB, Dowell C, Purushottam L, Skalicky JJ, McIntosh JM, Chou DH. (2021) Discovery of Methylene Thioacetal-Incorporated α-RgIA Analogues as Potent and Stable Antagonists of the Human α9β10 Nicotinic Acetylcholine Receptor for the Treatment of Neuropathic Pain J Med Chem 64:9513-9524

Internal links
Nucleic acids
Structure

External links

Tools