Spider venoms: a rich source of acylpolyamines and peptides as new leads for CNS drugs

Abstract

Advances in NMR and mass spectrometry as well as in peptide biochemistry coupled to modern methods in electrophysiology have permitted the isolation and identification of numerous products from spider venoms, previously explored due to technical limitations. The chemical composition of spider venoms is diverse, ranging from low molecular weight organic compounds such as acylpolyamines to complex peptides. First, acylpolyamines (< 1000 Da) have an aromatic moiety linked to a hydrophilic lateral chain. They were characterized for the first time in spider venoms and are ligand-gated ion channel antagonists, which block mainly postsynaptic glutamate receptors in invertebrate and vertebrate nervous systems. Acylpolyamines represent the vast majority of organic components from the spider venom. Acylpolyamine analogues have proven to suppress hippocampal epileptic discharges. Moreover, acylpolyamines could suppress excitatory postsynaptic currents inducing Ca+ accumulation in neurons leading to protection against a brain ischemic insult. Second, short spider peptides (< 6000 Da) modulate ionic currents in Ca2+, Na+, or K+ voltage-gated ion channels. Such peptides may contain from three to four disulfide bridges. Some spider peptides act specifically to discriminate among Ca2+, Na+, or K+ ion channel subtypes. Their selective affinities for ion channel subfamilies are functional for mapping excitable cells. Furthermore, several of these peptides have proven to hyperpolarize peripheral neurons, which are associated with supplying sensation to the skin and skeletal muscles. Some spider N-type calcium ion channel blockers may be important for the treatment of chronic pain. A special group of spider peptides are the amphipathic and positively charged peptides. Their secondary structure is alpha-helical and they insert into the lipid cell membrane of eukaryotic or prokaryotic cells leading to the formation of pores and subsequently depolarizing the cell membrane. Acylpolyamines and peptides from spider venoms represent an interesting source of molecules for the design of novel pharmaceutical drugs.

Pharmacological Characterization of the Edema Caused by Vitalius dubius (Theraphosidae, Mygalomorphae) Spider Venom in Rats

“…The venoms of these spiders contain a variety of toxins that target primarily ion channels (Escoubas, 2006;Estrada et al, 2007;Herzig et al, 2011). Despite their large size and intimidating appearance, most theraphosids show low aggressivity, and this has led to their popularity as pets, particularly in North America and Europe.…”

Enhancing Glutamate Transport: Mechanism of Action of Parawixin1, a Neuroprotective Compound from Parawixia bistriata Spider Venom

“…Because L-glutamate is the primary neurotransmitter at the insect neuromuscular junction and spiders paralyze their prey by interfering with glutamate neurotransmission (see reviews by Estrada et al, 2007) we previously tested the venom of a spider, Parawixia bistriata for its potential effects on glutamate receptors, transporters, and other modulators of glutamate transmission. In these studies we isolated a compound from this spider venom (Parawixin1, previously referred to as PbTx1.2.3) that could enhance glutamate uptake into cortical synaptosomes (Fontana et al, 2003).…”

Heteropoda Toxin 2 Interaction with Kv4.3 and Kv4.1 Reveals Differences in Gating Modification

“…Peptide toxins have found wide use as structural probes for ion channels and as pharmaceutical agents (Lewis and Garcia, 2003;Catterall et al, 2007;Estrada et al, 2007;Swartz, 2007;Hodgson and Isbister, 2009;Dutertre and Lewis, 2010). Their interaction with ion channels falls into two general classes: pore blockade, or gating modification.…”