Conotoxins that Confer Therapeutic Possibilities
Abstract
:1. Introduction
2. Conus Peptides That Exhibit Therapeutic Potential
2.1. Voltage-Gated Ion Channels Targeted by Conotoxins
2.1.1. Na+ Channel Inhibitors
Peptide | AA Sequence | Gene Family with Cysteine Framework and Residues | Targets | Has no Effect on | Reference |
---|---|---|---|---|---|
Lt5d | DCCPAKLLCCNP | T superfamily V [connectivity I–III, II–IV] -CC-CC- | Na+ channel | ND | [42] |
Lt6c | WPCKVAGSPCGLVSECCGTCNVLRNRCV | O1 superfamily VI/VII [connectivity I–IV, II–V, III–VI] -C-C-CC-C-C- | Na+ channel | ND | [43] |
TIIIA | RHGCCKGOKGCSSRECRPQHCC | M superfamily III -CC-C-C-CC- | rNav1.2 rNav1.4 | rNav1.3 rNav1.5 rNav1.7 rNav1.8 | [44] |
Cal12a | DVCDSLVGGHCIHNGCWCDQEAPHGNCCDTDGCTAAWWCPGTKWD | O2 superfamily XII -C-C-C-C-CC-C-C- | Na+ channel | ND | [45] |
Cal12b | DVCDSLVGGHCIHNGCWCDQDAPHGNCCDTDGCTAAWWCPGTKWD | O2 superfamily XII -C-C-C-C-CC-C-C- | Na+ channel | ND | [45] |
BuIIIA | VTDRCCKGKRECGRWCRDHSRCC | M superfamily III -CC-C-C-CC- | Nav1.4 | ND | [46] |
BuIIIB | VGERCCKNGKRGCGRWCRDHSRCC | M superfamily III -CC-C-C-CC- | Nav1.4 | ND | [46] |
BuIIIC | IVDRCCNKGNGKRGCSRWCRDHSRCC | M superfamily III -CC-C-C-CC- | Nav1.4 | ND | [46] |
SIIIA | ZNCCNGGCSSKWCRDHARCC | M superfamily III -CC-C-C-CC- | rNav1.2 rNav1.4 | rNav1.3 rNav1.5 rNav1.7 rNav1.8 | [47] |
SIIIB | ZNCCNGGCSSKWCKGHARCC | M superfamily III -CC-C-C-CC- | rNav1.2 rNav1.4 | rNav1.3 rNav1.5 rNav1.7 rNav1.8 | [47] |
2.1.2. Ca2+ Channel Inhibitors
Peptide | AA Sequence | Gene Family with Cysteine Framework and Residues | Targets | Has no Effect on | Reference |
---|---|---|---|---|---|
CalTx | NCPAGCRSQGCCM | XVI -C-C-CC- | N-type L-type P/Q-type R-type | T-type | [49] |
FVIA | CKGTGKSCSRIAYNCCTGSCRSGKC | O1 superfamily VI/VII [connectivity I–IV, II–V, III–VI] -C-C-CC-C-C- | N-type | T-type P/Q-type TTX-S Na+ channel | [48] |
2.1.3. K+ Channel Inhibitors
Peptide | AA Sequence | Gene Family with Cysteine Framework and Residues | Targets | Has no Effect on | Reference |
---|---|---|---|---|---|
Sr11a | NQQCCWRSCCRGECEAPCRFGP | I2 superfamily XI [connectivity I–IV, II–VI, III–VII, V–VIII] -CC-CC-C-C- | Kv1.2 Kv1.6 | Kv1.3 | [50,51] |
RIIIj | LPPCCTPPKKHCPAPACKYKPCCKS | M superfamily III -CC-C-C-CC- | Kv1.2 | Kv1.1 Kv1.3 Kv1.4 Kv1.5 Kv1.6 KCNQ2/KCNQ3 BK | [20] |
2.2. Ligand-Gated Ion Channels Targeted by Conotoxins
nAChR Inhibitors
Peptide | AA Sequence | Gene Family with Cysteine Framework and Residues | nAChR Targets | Has no Effect on | Reference |
---|---|---|---|---|---|
AlphaD-cap | EVQECQVDTPGSSWGKCCMTRMCGTMCCSRSVCTCVYHWRRGHGCSCPG | D superfamily XX -C-CC-C-CC-C-C-C-C- | α7 α3β2 α4β2 | α3β4 α4β4 | [57] |
AlphaD-mus | DVRECQVNTPGSKWGKCCMTRMCGTMCCARSGCTCVYHWRRGHGCSCPG | D superfamily XX -C-CC-C-CC-C-C-C-C- | α7 α3β2 α4β2 | α3β4 α4β4 | [57] |
α-PIB | ZSOGCCWNPACVKNRC | A superfamily I [connectivity I–III, II–IV] -CC-C-C- | α1β1εδ α1β1γδ | α7 α3β4 α3β2 α2β4 α9α10 | [63] |
SrIA | RTCCSROTCRMγYPγLCG | A superfamily I [connectivity I–III, II–IV] -CC-C-C- | α4β2 α1β1γδ | α3β4 | [64] |
SrIB | RTCCSROTCRMEYPγLCG | A superfamily I [connectivity I-III, II-IV] -CC-C-C- | α4β2 α1β1γδ | α3β4 | [64] |
Pu14a | DCPPHPVPGMHKCVCLKTC | A superfamily XIV [connectivity I–III, II–IV] -C-C-C-C- | α3β2 α6α3β2 α1β1γδ | K+ channels | [62] |
PrIIIE | AARCCTYHGSCLKEKCRRKYCCGR | M superfamily III -CC-C-C-CC- | α1β1εδ α1β1γδ | Nav1.4 | [60] |
ArIA | IRDECCSNPACRVNNOHVCRRR | A superfamily I [connectivity I-III, II-IV] -CC-C-C- | α7 α3β2 | ND | [68] |
ArIB | DECCSNPACRVNNPHVCRRR | A superfamily I [connectivity I-III, II-IV] -CC-C-C- | α7 α3β2 | ND | [68] |
Ac1.1a | NGRCCHPACGKHFNCGR | A superfamily I [connectivity I-III, II-IV] -CC-C-C- | α1β1γδ α1β1εδ α2β2 α3β4 α1γβ1 | ND | [66,67] |
Ac1.1b | NGRCCHPACGKHFNCGR | A superfamily I [connectivity I-III, II-IV] -CC-C-C- | α1β1εδ α1β1γδ α2β2 α3β4 α1γβ1 | ND | [66,67] |
PrXA | TYGIYDAKPOFSCAGLRGGCVLPONLROKFKE | -C-C- | α1β1εδ α1β1γδ | α7 α3β2 α3β4 α2β4 α4β2 α9 α10 Nav1.4 Nav1.6 NR2A NR2B | [59] |
α-TxIA | GCCSRPPCIANNPDLC | A superfamily I [connectivity I-III, II-IV] -CC-C-C- | α7 α3β2 | α4β2 α1β1εδ α1β1γδ | [69] |
TxIA(A10L) | GCCSRPPCILNNPDLC | A superfamily I [connectivity I-III, II-IV] -CC-C-C- | α7 α3β2 | α4β2 α1β1εδ α1β1γδ | [69] |
3. Prediction of Conotoxin Targets
4. Literature Analysis of Conotoxins Suggest Specific Therapeutic Potential
5. Concluding Remarks
References
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Essack, M.; Bajic, V.B.; Archer, J.A.C. Conotoxins that Confer Therapeutic Possibilities. Mar. Drugs 2012, 10, 1244-1265. https://doi.org/10.3390/md10061244
Essack M, Bajic VB, Archer JAC. Conotoxins that Confer Therapeutic Possibilities. Marine Drugs. 2012; 10(6):1244-1265. https://doi.org/10.3390/md10061244
Chicago/Turabian StyleEssack, Magbubah, Vladimir B. Bajic, and John A. C. Archer. 2012. "Conotoxins that Confer Therapeutic Possibilities" Marine Drugs 10, no. 6: 1244-1265. https://doi.org/10.3390/md10061244