Tarantulas: eight-legged pharmacists and combinatorial chemists

A verified bite by Heteroscodra maculata (Togo starburst or ornamental baboon tarantula) resulting in long-lasting muscle cramps

“…maculata is an agile and fast tree dwelling theraphosid spider native to western Africa. For other tree dwelling species like Poecilotheria, the specific toxicity has been suggested to be necessary to quickly and efficiently paralyze their large and struggling prey in an aerial environment without the help of an immobilizing web [3], so this might apply to H. maculata as well. One toxin in their venom, heteroscodratoxin 1 (HmTx1), has been found to inhibit voltage-dependent potassium channels (the Kv2.2-subtype found in neurons in the brain) and immediately induce convulsions in mice.…”

Spider toxins comprising disulfide‐rich and linear amphipathic domains: a new class of molecules identified in the lynx spider Oxyopes takobius

“…This signature may be reduced to the more general principal structural motif CX 6 CX n CC (C 1 X 6 C 2 X 5 C 4 C 5 in our case), and extra structural motif CXCX n CXC (C 6 XC 7 X m C 8 XC 9 in our case) that are characteristic of spider neurotoxins [23]. The principal structural motif and the extra structural motif in turn conform to the more general ICK motif CX 2-7 CX 3-11 CX 0-7 CX 1-17 CX [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] …”

“…At present, the known spider venom compounds are conventionally split into three categories: (a) lowmolecular-mass chemicals of diverse nature (from simple compounds sich as salts to elaborate molecules such as acylpolyamines [7,8]), (b) peptides (up to 10 kDa), and (c) proteins [9]. The peptidic component is the most abundant and functionally important in most investigated species, and peptides may come in two types: (a) neurotoxins, which are usually rich in disulfide bridges and conform to the inhibitor cystine knot (ICK/knottin) fold [10], and (b) cytotoxins, which are typically linear peptides that adopt a helical conformation upon interaction with lipid membranes [11]. The latter group are also referred to as membraneactive peptides (MAPs) or antimicrobial peptides (AMPs) due to the activities of these molecules.…”

Venomics as a drug discovery platform

“…Invertebrate venoms mostly contain a large array of polypeptides, 1-10 kDa in size, most of them tightly folded and stabilized by several disulfide bridges [3]. Conversely, snake venoms contain proteins belonging to several structural classes, such as peptides, small neurotoxins, phospholipases and various enzymes [4].…”