MARINE CYSTINE KNOT PEPTIDES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A 35-residue cystine knot peptide with a unique pyroglutamic acid N-terminus has been isolated from a unique marine invertebrate taxonomically distinct from the well known conotoxin producing cone snails. This discovery provides strong evidence for a microbial symbiont that produces this class of peptide which has been of significant interest to the drug discovery community. The detailed structure assignment of this peptide will be important for comparison to known cystine knot peptides like the conotoxins and various terrestrial venoms to determine if it may have any interactions with known biological targets. Chemical methods including enzymatic and partial reductions/alkylations have been attempted to establish the locations of the dissulfide linkages but have failed. In addition to improving the overall prediction of the peptide in silico, high field NMR will provide the necessary resolution to determine the arrangements of critical structural features.