Tarantulas: eight-legged pharmacists and combinatorial chemists

Area of Science:

• Biochemistry
• Pharmacology
• Molecular Biology

Background:

• Tarantula venoms are rich sources of novel ligands targeting cell receptors and ion channels.
• The pharmacological diversity of tarantula venom peptides remains largely unexplored.
• Over 55 tarantula venoms have undergone initial investigations.

Purpose of the Study:

• To explore the pharmacological and structural diversity of tarantula venom peptides.
• To describe the properties and biological activities of known tarantula toxins.
• To investigate the therapeutic potential and evolutionary significance of these toxins.

Main Methods:

• Pharmacological and toxicological investigations.
• Mass spectrometry, specifically MALDI-TOF MS, for peptide analysis.
• Structural analysis of known peptide toxins.

Main Results:

• Tarantula venom toxins are typically small peptides with limited structural patterns.
• Most known toxins adopt the Inhibitory Cystine Knot (ICK) motif, with variations in loop lengths.
• Some toxins utilize an elaborated Disulfide-Directed beta-Hairpin (DDH) motif, related to the ICK fold.
• Structure-activity relationships highlight the importance of surface features for toxin specificity.
• Toxins acting on voltage-gated ion channels and pore-blocking toxins show conserved mechanisms.

Conclusions:

• Tarantula venom peptides exhibit remarkable structural and functional diversity.
• The ICK and DDH motifs provide versatile scaffolds for toxin evolution and function.
• Tarantulas are valuable models for discovering novel therapeutic agents.
• These toxins offer insights into molecular evolution and ion channel interactions.