From Mollusks to Medicine: A Venomics Approach for the Discovery and Characterization of Therapeutics from Terebridae Peptide Toxins.
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.
Hunter College, The City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. averdes@gradcenter.cuny.edu.|The Graduate Center, City University of New York, 365 5th Ave, New York, NY 10016, USA. averdes@gradcenter.cuny.edu.|Sackler Institute for Comparative Genomics, Invertebrate Zoology, American Museum of Natural History, Central Park West &amp; 79th St, New York, NY 10024, USA. averdes@gradcenter.cuny.edu.
Aida
A
Verdes
Hunter College, The City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. panand@hunter.cuny.edu.
Prachi
P
Anand
Hunter College, The City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. jgorson@gradcenter.cuny.edu.|The Graduate Center, City University of New York, 365 5th Ave, New York, NY 10016, USA. jgorson@gradcenter.cuny.edu.|Sackler Institute for Comparative Genomics, Invertebrate Zoology, American Museum of Natural History, Central Park West &amp; 79th St, New York, NY 10024, USA. jgorson@gradcenter.cuny.edu.
Juliette
J
Gorson
Hunter College, The City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. sjannetti@gradcenter.cuny.edu.|The Graduate Center, City University of New York, 365 5th Ave, New York, NY 10016, USA. sjannetti@gradcenter.cuny.edu.
Stephen
S
Jannetti
Hunter College, The City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. mkelly3@gradcenter.cuny.edu.|The Graduate Center, City University of New York, 365 5th Ave, New York, NY 10016, USA. mkelly3@gradcenter.cuny.edu.
Patrick
P
Kelly
Hunter College, The City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. ael355@nyu.edu.|Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine 550 1st Avenue, New York, NY 10016, USA. ael355@nyu.edu.
Abba
A
Leffler
Hunter College, The City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. cs4379@nyu.edu.|Tandon School of Engineering, New York University 6 MetroTech Center, Brooklyn, NY 11201, USA. cs4379@nyu.edu.
Danny
D
Simpson
Hunter College, The City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. girish.ramrattan22@myhunter.cuny.edu.
Girish
G
Ramrattan
Hunter College, The City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. mholford@hunter.cuny.edu.|The Graduate Center, City University of New York, 365 5th Ave, New York, NY 10016, USA. mholford@hunter.cuny.edu.|Sackler Institute for Comparative Genomics, Invertebrate Zoology, American Museum of Natural History, Central Park West &amp; 79th St, New York, NY 10024, USA. mholford@hunter.cuny.edu.
Mandë
M
Holford
D000818:Animals; D055808:Drug Discovery; D015394:Molecular Structure; D008974:Mollusca / Q000235:genetics; D008978:Mollusk Venoms / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use / Q000633:toxicity; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use / Q000633:toxicity; D010802:Phylogeny
D008978:Mollusk Venoms; D010455:Peptides
Terebridae; animal venom; drug delivery; drug development; drug discovery; peptide therapeutics; peptide toxins; teretoxins; venom peptides; venomics