Sample limited characterization of a novel disulfide-rich venom peptide toxin from terebrid marine snail Terebra variegata.
Disulfide-rich peptide toxins found in the secretions of venomous organisms such as snakes, spiders, scorpions, leeches, and marine snails are highly efficient and effective tools for novel therapeutic drug development. Venom peptide toxins have been used extensively to characterize ion channels in the nervous system and platelet aggregation in haemostatic systems. A significant hurdle in characterizing disulfide-rich peptide toxins from venomous animals is obtaining significant quantities needed for sequence and structural analyses. Presented here is a strategy for the structural characterization of venom peptide toxins from sample limited (4 ng) specimens via direct mass spectrometry sequencing, chemical synthesis and NMR structure elucidation. Using this integrated approach, venom peptide Tv1 from Terebra variegata was discovered. Tv1 displays a unique fold not witnessed in prior snail neuropeptides. The novel structural features found for Tv1 suggest that the terebrid pool of peptide toxins may target different neuronal agents with varying specificities compared to previously characterized snail neuropeptides.
Department of Chemistry and Biochemistry, City University of New York- Hunter College and Graduate Center, New York, New York, United States of America.
Prachi
P
Anand
Department of Chemistry and Biochemistry, City University of New York- Hunter College and Graduate Center, New York, New York, United States of America.
Alexandre
A
Grigoryan
Department of Chemistry, College of Staten Island and Graduate Center, City University of New York, Staten Island, New York, United States of America.
Mohammed H
MH
Bhuiyan
NYU Langone Medical Center, New York University, New York, New York, United States of America.
Beatrix
B
Ueberheide
Department of Chemistry and Biochemistry, City University of New York- Hunter College and Graduate Center, New York, New York, United States of America.
Victoria
V
Russell
Department of Chemistry and Biochemistry, City University of New York- Hunter College and Graduate Center, New York, New York, United States of America.
Jose
J
Quinoñez
Department of Chemistry and Biochemistry, City University of New York- Hunter College and Graduate Center, New York, New York, United States of America.
Patrick
P
Moy
The Rockefeller University, New York, New York, United States of America.
Brian T
BT
Chait
Department of Chemistry, College of Staten Island and Graduate Center, City University of New York, Staten Island, New York, United States of America.
Sébastien F
SF
Poget
Department of Chemistry and Biochemistry, City University of New York- Hunter College and Graduate Center, New York, New York, United States of America; The American Museum of Natural History, New York, New York, United States of America.
Mandë
M
Holford
D000818:Animals; D004220:Disulfides / Q000032:analysis*; D049851:Gastropoda; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010455:Peptides / Q000737:chemistry*; D014118:Toxins, Biological / Q000737:chemistry*; D014688:Venoms / Q000737:chemistry*
D004220:Disulfides; D010455:Peptides; D014118:Toxins, Biological; D014688:Venoms