In the picture: disulfide-poor conopeptides, a class of pharmacologically interesting compounds

Abstract

During evolution, nature has embraced different strategies for species to survive. One strategy, applied by predators as diverse as snakes, scorpions, sea anemones and cone snails, is using venom to immobilize or kill a prey. This venom offers a unique and extensive source of chemical diversity as it is driven by the evolutionary pressure to improve prey capture and/or to protect their species. Cone snail venom is an example of the remarkable diversity in pharmacologically active small peptides that venoms can consist of. These venom peptides, called conopeptides, are classified into two main groups based on the number of cysteine residues, namely disulfide-rich and disulfide-poor conopeptides. Since disulfide-poor conotoxins are minor components of this venom cocktail, the number of identified peptides and the characterization of these peptides is far outclassed by its cysteine-rich equivalents. This review provides an overview of 12 families of disulfide-poor peptides identified to date as well as the state of affairs.

Conomarphins cause paralysis in mollusk: Critical and tunable structural elements for bioactivity

“…Conopeptides are distinguished by their posttranslational modifications (PTMs) such as oxidation of multiple Cys residues to create elaborate disulfide linkages. Disulfide‐rich conopeptides, referred to as conotoxins, represent the majority of known conopeptides to date with a wide range of biological targets . Disulfide‐poor conopeptides, those with <2 disulfide bonds, have been recognized to be an equally important component of the venom arsenal of Conoidean snails.…”

“…Disulfide‐poor conopeptides, those with <2 disulfide bonds, have been recognized to be an equally important component of the venom arsenal of Conoidean snails. Among the recognized disulfide‐poor conopeptides are conantokins, contulakins, conorfamides conophans, conomap, conolysin, conoGAY, conoCAP, cono‐NPY, and conomarphins …”

“…Highly conserved features of conomarphins include the (A/T)(H/N)P and NS(W/F)W(T/S) motifs at positions 6 to 8 and 11 to 15, respectively. Epimerization of the aromatic amino acid at position 13 and proline hydroxylation at position 10 are common posttranslational modifications among conomarphins . Solution structure analysis of conomarphin from C. marmoreus indicated the importance of the conserved residues and posttranslational modifications for higher order structure.…”

“…Disulfide-rich conopeptides, referred to as conotoxins, represent the majority of known conopeptides to date with a wide range of biological targets. 12,13 Disulfide-poor conopeptides, those with <2 disulfide bonds, have been recognized to be an equally important component of the venom arsenal of Conoidean snails. Among the recognized disulfide-poor conopeptides are conantokins, contulakins, conorfamides conophans, conomap, conolysin, conoGAY, conoCAP, cono-NPY, and conomarphins.…”

“…Among the recognized disulfide-poor conopeptides are conantokins, contulakins, conorfamides conophans, conomap, conolysin, conoGAY, conoCAP, cono-NPY, and conomarphins. 13 The conomarphins are a group of short conopeptides with no disulfide bonds belonging to the M-superfamily. There are 12 known conomarphins, based on peptide and nucleic acid evidence, with little structural similarity to the mature sequence of other conopeptides in the M-superfamily.…”