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.
Highlights
Medicinal treatments have a storied history tied to natural products discovery and development.Natural products derived from plants and animals have been the source of traditional medicine for millennia, and more recently have become major sources of chemical diversity as drug leads, driving research efforts in pharmaceutical drug discovery and development [1,2]
This venomics-based discovery strategy takes into account different characteristics, such as the presence of a venom apparatus, and demonstrates the importance of understanding phylogeny to enhance the identification of venom peptides with potential pharmacological applications [19]
Recombinant expression thethe synthesis of peptides thatthat are Recombinant expression techniques techniquesare areaagreat greatalternative alternativeforfor synthesis of peptides problematic for due to length or complexity, such as many teretoxins, which can have a length are problematic for solid-phase peptide synthesis (SPPS) due to length or complexity, such as many teretoxins, which can have up to 70 acids
Summary
Medicinal treatments have a storied history tied to natural products discovery and development. Due to technological constraints, such as size and ease of collection, venomous organisms peptides are predominantly being investigated for the development of drug therapies targeted tolike ion snakes channels have and receptors [12,13,14,15,16]. The most promising avenue to overcome these challenges is to apply interdisciplinary strategies that integrate molecular biology and biochemical analyses of venom compounds to optimize the characterization of peptides [41] This strategy, often referred to as venomics, combines classic approaches for the study of biodiversity, such as taxonomy and phylogeny, with modern NGS techniques and proteomic methods, creating a robust evolutionary roadmap for effective drug discovery while greatly advancing knowledge on venom systematics and evolution [16,19,42,43,44]. We describe our specific venomics approach to investigate Terebridae diversity and evolution, and to identify and characterize teretoxins and their potential for biomedical applications, paving the scientific route from mollusks to medicine (Figure 1)
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