Table 1.
The conopeptide sequences derived from C. geographus – pharmacological targeting, affinity, origin and expression within the milked venom.
| Name | Amino acid sequence | Target | Affinity IC50 [nM] |
Original source |
Monoisotopic mass (Da) |
Observed m/z in MV |
RP-HPLC Rt (min)a |
Ref.b |
|---|---|---|---|---|---|---|---|---|
| Lys-conopressin G | CFIRNCPKG* | Vasopressin Receptor | N.D. | DV | 1033.49 | 1034.48 | N.D. | [1] |
| α-GII | ECCHPACGKHFSC* | nAChRb | N.D. (LD50 12 μg/kg; mouse) | DV | 1415.5 | 1416.43 | 32.3d | [2] |
| α-GI | ECCNPACGRHYSC* | DV | 1436.48 | 1437.41 | 32.3 | [2] | ||
| nAChR (mouse) | 20 | |||||||
| Site 1 (αδ) | 1.3 ± 0.3 | |||||||
| G5.1 | QGWCCKENIACCV | N.D. | N.D | cDNA | 1451.54 | – | – | [3] |
| α-GIC | GCCSHPACAGNNQHIC* | nAChR (human) | cDNA | 1608.58 | – | – | [4] | |
| hα3β2 | 1.1 | |||||||
| hα3β4 | 775 | |||||||
| hα4β2 | 309 | |||||||
| G1.1 | ECCNPACGRHYSCKG | nAchRb | N.D | cDNA | 1622.58 | 1622.55 | N.D. | [3] |
| α-GIA | ECCNPACGRHYSCGK | nAchRb | N.D | DV | 1622.58 | 1622.55 | 31.0 | [2] |
| Contulakin-G | ZSEEGGSNATKKPYIL | Neurotensin Receptor | DV | 2068.97 | 2068.11 | N.D. | [5] | |
| NTR2 (human) | 960 | |||||||
| NTR3 (mouse) | 250 | |||||||
| α-GID | IRDγCCSNPACRVNNOHVC | nAchR rα7(rat) | 4.5 | DV | 2185.86 | – | – | [6] |
| hα3β2 | 3.1 | |||||||
| hα4β2 | 152 | |||||||
| Conantokin-G | GEγγLQγNQγLIRγKSN* | NMDA Receptor | DV | 2262.94 | – | – | [7, 8] | |
| NR2B | 480 | |||||||
| Brain (human) | 21–69 | |||||||
| μ-GIIIC | RDCCTOOKKCKDRRCKOLKCCA* | NaVc | N.D. | DV | 2595.2 | 2595.02 | 26.4d | [9, 10] |
| μ-GIIIA | RDCCTOOKKCKDRQCKOQRCCA* | NaV1,4 | DV | 2610.14 | 2610.08 | 26.4 | [10, 11, 12] | |
| Brain (rat) | 69.2 ± 0.8 | |||||||
| Brain (chicken) | >1000 | |||||||
| Skeletal muscle (rat) | 0.97 ± 0.17 | |||||||
| Electroplax (eel) | 3.48 ± 0.09 | |||||||
| μ-GIIIB | RDCCTOORKCKDRRCKOMKCCA* | NaV1,4 | DV | 2641.16 | – | – | [10, 13, 14] | |
| NaV1.4 (human) | 1065 | |||||||
| NaV1.4 (rat) | 49 | |||||||
| NaV1.4 (eel) | 1.1 ± 0.1 | |||||||
| ω-GVIC | CKSOGSSCSOTSYNCCRSCNOYTKRC | NaVb | N.D. | DV | 2875.99 | – | – | [10] |
| ω-GVIA | CKSOGSSCSOTSYNCCRSCNOYTKRCY* | CaV 2.2 (chick brain) | 0.15 | DV | 3038.17 | 3038.09 | 32.8 | [10, 15] |
| CaV 2.2 (mouse brain) | 0.07 | |||||||
| ω-GVIB | CKSOGSSCSOTSYNCCRSCNOYTKRCYG | CaVb | N.D. | DV | 3096.13 | 3096.02 | 33.5 | [10] |
| ω-GVIIB | CKSOGTOCSRGMRDCCTSCLSYSNKCRRY | CaVb | N.D. | DV | 3289.34 | – | – | [10] |
| Scratcher peptide | KFLSGGFKγIVCHRYCAKGIAKEFCNCPD* | N.D. | N.D. | DV | 3301.53 | – | – | [15] |
| ω-GVIIA | CKSOGTOCSRGMRDCCTSCLLYSNKCRRY | CaV 2.2 | 3.7 | DV | 3315.39 | 3315.25 | 36.8 | [10, 16] |
| G6.1 | DDECEPPGDFCGFFKIGPPCCSGWCFLWCA | N.D. | N.D. | cDNA | 3322.24 | 3322.13 | N.D. | [3] |
| Conotoxin-GS | ACSGRGSRCOOQCCMGLRCGRGNPQKCIGAHγDV | NaV Skeletal muscle (rat) | 880 | DV | 3617.5 | – | – | [17] |
| Sequence 401 from Patent EP1852440 | SDGGNAAAKESDVIALTVWKCCTIPSC YEKKKIKACVF | N.D. | N.D. | cDNA | 4071.99 | – | – | [18] |
| Sequence 323 from Patent EP1852440 | SDGRNAAANDQASDLMAATVRGCC AVPSCRLRNPDLCGGGR | N.D. | N.D. | cDNA | 4143.86 | – | – | [18] |
| σ-GVIIIA | GCTRTCGGOKCTGTCTCTNSSKCGC RYNVHPSGWGCGCACS* | 5-HT3 | 53 ± 3 | DV | 4189.43 | – | – | [19] |
| Sequence 321 from Patent EP1852440 | SDGRNDAAKAFDLISSTVKKGCCSHPAC AGNNQHICGRRR | N.D. | N.D. | cDNA | 4238.98 | – | – | [18] |
= C-terminal amidation; Z = pyroglutamic acid; S = O-linked glycosylated serine; w = D-tryptophan; W = bromotryptophan; O = 4-trans-hydroxyproline; T = glycosylated threonine; γ = gamma-carboxy glutamic acid; Y = sulfotyrosine.
RP-HPLC retentions are in reference to Fig. 1A.
Corresponding references listed in Supplemental Materials.
Targeting assigned based on sequence homology; N.D., Not Determined, DV, Duct Venom; MV, Milked Venom; cDNA, complementary DNA; nAChR, nicotinic Acetylcholine Receptor; NMDA, N-Methyl-d-aspartate; CaV, Voltage gated calcium channels; NaV Voltage gated sodium channels; 5-HT3, Serotonin 5-HT3-receptor.
Observed as shoulder in primary peak.