芋螺屬(Conus)的掠食性海螺迄今估計已有700多種，生活在熱帶的淺水域中，棲息的環境從沙岸、泥岸、岩礁岸均有，平常晝伏夜出，多以肉食為主。這些螺類體呈錐形，屬於腹足綱軟體動物，以獨特的獵食結構——含有毒液的類魚叉箭狀齒舌，捕食或抵禦環節動物(如沙蠶、海濱蚯蚓等)、魚類、甚至其他的軟體動物。每一種芋螺的毒液多是由超過50種以上富含雙硫鍵的芋螺毒素(conotoxins)組合而成，分別對動物鈣、鈉、鉀離子通道或菸鹼性乙醯膽鹼受體產生藥理性抑制作用，進而影響神經傳導。芋螺毒素對不同離子通道或受體廣泛地選擇抑制，具有精細的專一性，可用以分辨其亞型。化學家與藥理學家以分子神經生物學的方法偵測芋螺毒素，首先發現它們能減緩痛覺刺激的反應，因此開啟藥物發展的潛力。我們為了解芋螺的生物背景、已知的芋螺毒素及醫藥應用，將芋螺的生物學與演化、芋螺毒素的命名、分類、結構、神經毒理機制、轉譯後修飾、臨床應用與其他毒素之比較，既存的資料庫，彙整成最完備並可查詢的生物資訊資料庫，提供研究者一個便利的研究工具。

Predatory shallow-water tropical marine snails within the genus Conus are estimated to consist of up to 700 species. These carnivorous mollusks have devised efficient venom harpoon-like radular teeth that allow them to predominantly incapacitate polychaete annelids (vermivores), in some cases fish (piscivores), or other mollusks (molluscivores) as an envenomation survival strategy for feeding, defense, and competitor deterrence. The venom of each Conus species contains a distinctive assortment of over 50 diversified disulfide-rich conotoxins with varied pharmacological specificities that selectively inhibit the function of ion channels (Ca2+, Na+, K+) or nicotinic acetylcholine receptors (nAChRs) involved in the animal neurotransmission. Across the genus Conus, the conotoxins represent an extensive array of ion channel blockers each showing an exquisite selectivity to distinguish between channels / receptors and even particular their subtypes. Novel conotoxins detected in the molecular neurobiological approach, providing chemists and pharmacologists a vast library (>50,000 individual toxins) of conotoxins have been further screened for their abilities to modify the responses of tissues to pain stimuli as a first step in describing their potential as lead compounds for novel drugs. In this article, we present the natural history of the Conus biology as well as the nomenclature, classification, structure, neurotoxicological mechanisms, post-translational modification, and pharmaceutical applications of conotoxins. In addition, we also set up the bioinformatic database and search engine about hitherto-identified name and distribution of Conus species and neuropharmacological mechanism, accession number, sequence, and 3D structure of conotoxins and provide researchers advantageous tools for further investigation.

Chinese Abstract………………………………………………………I
English Abstract………………………………………………………II
Abbreviations…………………………………………………………III
I.Introduction: Conotoxin and Cone Snail Overview……………1
II.Perspectives of Cone Snails……………………………………5
A.Biology of cone snails……………………………………………5
1.Life Cycle of Conus………………………………………………5
2.Morphology and Anatomy……………………………………………6
3.Distribution and habit……………………………………………8
4.Phylogenetic and taxonomic classification…………………9
III.Conotoxin and Receptor………………………………………13
A.Venom apparatus and hunt mechanism…………………………13
B.Venom composition, nomenclature, and biochemistry ……15
C.Molecular role of Conus venoms in mollusks………………18
IV.Structural Genomics and Structure of Conopeptides……………20
A.Organization of conopeptide gene structure………………20
B.Characterization of conopeptide structure and biology…………………20
1.α-Conotoxins………………………………………………………21
2.μ-Conotoxins………………………………………………………28
3.ω-Conotoxins………………………………………………………30
4.δ-Conotoxins………………………………………………………33
5.μO-Conotoxins………………………………………………………36
6.κ-Conotoxins………………………………………………………38
C.Conotoxin regioisomeric folding……………………………42
D.Post-translational modification……………………………43
V.Pharmaceutical Applications of Conopeptides……………50
A.Ion channels as targets for toxins………………………50
1.Nicotinic Acetylcholine Receptor (nAChR)-Channels……50
2.Calcium Channels………………………………………………51
3.Sodium Channels…………………………………………………52
4.Potassium Channels…………………………………………53
B.Neuropharmacological effects……………………………54
C.Drug design as potential therapeutic agents………59
D.Molecular probes for neurological disorders………62
1.Epilepsy………………………………………………62
2.Parkinson’s disease………………………………64
3.Alzheimer's disease…………………………………65
4.Ischemic stroke………………………………………66
5.Myasthenia gravis……………………………………67
6.Lambert-Eaton Myasthenic syndrome (LEMS)……67
VI.Database of Conotoxins……………………………69
A.Review of cone snail and conotoxin databases…69
B.Conotoxin database……………………………………72
VII.Results and Discussion……………………………74
A.Conotoxins and venom peptides from other species…74
B.Rationale of conotoxin cabal……………………………75
C.Conus molecular neuroscience……………………………76
D.The complexity of conotoxins……………………………77
E.Conotoxins as sources of drug leads…………………78
F.Toxin mechanic pathway and toxic models……………79
VIII.References………………………………………………82
IX.Tables………………………………………………………97
Table 1………………………………………………………97
Table 2………………………………………………………108
Table 3………………………………………………………110
Table 4………………………………………………………112
Table 5………………………………………………………113
Table 6………………………………………………………115
Table 7………………………………………………………117
X.Figures……………………………………………………120
Figure 1……………………………………………………120
Figure 2……………………………………………………121
Figure 3……………………………………………………122
Figure 4……………………………………………………123
Figure 5……………………………………………………124
Figure 6……………………………………………………125
Figure 7……………………………………………………126
Figure 8……………………………………………………127
Figure 9……………………………………………………129
Figure 10…………………………………………………130
Figure 11…………………………………………………131
Figure 12…………………………………………………132
Figure 13…………………………………………………133
Figure 14…………………………………………………134
Figure 15…………………………………………………135
Figure 16…………………………………………………136
Figure 17…………………………………………………137
Figure 18…………………………………………………138
Figure 19…………………………………………………139
Figure 20…………………………………………………141
Figure 21…………………………………………………142
XI.Appendix………………………………………………143
Appendix 1………………………………………………143
Appendix 2………………………………………………144

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