From Mollusks to Medicine: A Venomics Approach for the Discovery and Characterization of Therapeutics from Terebridae Peptide Toxins

Toxins (Basel). 2016 Apr 19;8(4):117. doi: 10.3390/toxins8040117.

Abstract

Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1) delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2) identification and classification of putative teretoxins through omics methodologies, including genomics, transcriptomics, and proteomics; (3) chemical and recombinant synthesis of promising peptide toxins; (4) structural characterization through experimental and computational methods; (5) determination of teretoxin bioactivity and molecular function through biological assays and computational modeling; (6) optimization of peptide toxin affinity and selectivity to molecular target; and (7) development of strategies for effective delivery of venom peptide therapeutics. While our research focuses on terebrids, the venomics approach outlined here can be applied to the discovery and characterization of peptide toxins from any venomous taxa.

Keywords: Terebridae; animal venom; drug delivery; drug development; drug discovery; peptide therapeutics; peptide toxins; teretoxins; venom peptides; venomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Drug Discovery
  • Molecular Structure
  • Mollusca / genetics
  • Mollusk Venoms* / chemistry
  • Mollusk Venoms* / genetics
  • Mollusk Venoms* / therapeutic use
  • Mollusk Venoms* / toxicity
  • Peptides* / chemistry
  • Peptides* / genetics
  • Peptides* / therapeutic use
  • Peptides* / toxicity
  • Phylogeny

Substances

  • Mollusk Venoms
  • Peptides