Abstract
Cone snail venoms provide an ideal resource for neuropharmacological tools and drug candidates discovery, which have become a research hotspot in neuroscience and new drug development. More than 1,000,000 natural peptides are produced by cone snails, but less than 0.1% of the estimated conotoxins has been characterized to date. Hence, the discovery of novel conotoxins from the huge conotoxin resources with high-throughput and sensitive methods becomes a crucial key for the conotoxin-based drug development. In this review, we introduce the discovery methodology of new conotoxins from various Conus species. It focuses on obtaining full N- to C-terminal sequences, regardless of disulfide bond connectivity through crude venom purification, conotoxin precusor gene cloning, venom duct transcriptomics, venom proteomics and multi-omic methods. The protocols, advantages, disadvantages, and developments of different approaches during the last decade are summarized and the promising prospects are discussed as well.
Highlights
Cone snails (Conus) are carnivorous mollusks from the Conidae family (Figure 1)
We introduced the discovery methodology of novel conotoxins from various Conus species
It focused on obtaining full N- to C-terminal sequences, regardless of disulfide connectivity through crude venom purification, conotoxin precursor gene cloning, venom duct transcriptomics, venom proteomics, and multi-omic methods
Summary
Cone snails (Conus) are carnivorous mollusks from the Conidae family (Figure 1). They live in the tropical oceans around the world and hunt fish (piscivorous), worms (vermivorous), or molluscs (molluscivorous) for food, they are slow-moving creatures [1]. Cone snails have evolved a full set of specialized envenomation apparatus to release bioactive venoms to compensate their slow movement for fast-moving prey, competitors, or/and predators [2,3]. Studies have confirmed that these bioactive venoms are a cocktail of neuroactive peptides, termed conopeptides or conotoxins, which can cause paralysis, shudder, and even death of the prey within seconds [1,5]. 2018, 16,and x heart disease [30,31], so on [32,33,34]
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