| http://purl.uniprot.org/citations/18831583 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18831583 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18831583 | http://www.w3.org/2000/01/rdf-schema#comment | "Disulfide-rich peptides represent a megadiverse group of natural products with very promising therapeutic potential. To accelerate their functional characterization, high-throughput chemical synthesis and folding methods are required, including efficient mapping of multiple disulfide bridges. Here, we describe a novel approach for such mapping and apply it to a three-disulfide-bridged conotoxin, mu-SxIIIA (from the venom of Conus striolatus), whose discovery is also reported here for the first time. Mu-SxIIIA was chemically synthesized with three cysteine residues labeled 100% with (15)N/(13)C, while the remaining three cysteine residues were incorporated using a mixture of 70%/30% unlabeled/labeled Fmoc-protected residues. After oxidative folding, the major product was analyzed by NMR spectroscopy. Sequence-specific resonance assignments for the isotope-enriched Cys residues were determined with 2D versions of standard triple-resonance ((1)H, (13)C, (15)N) NMR experiments and 2D [(13)C, (1)H] HSQC. Disulfide patterns were directly determined with cross-disulfide NOEs confirming that the oxidation product had the disulfide connectivities characteristic of mu-conotoxins. Mu-SxIIIA was found to be a potent blocker of the sodium channel subtype Na(V)1.4 (IC50 = 7 nM). These results suggest that differential incorporation of isotope-labeled cysteine residues is an efficient strategy to map disulfides and should facilitate the discovery and structure-function studies of many bioactive peptides."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.org/dc/terms/identifier | "doi:10.1021/ja804303p"xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.org/dc/terms/identifier | "doi:10.1021/ja804303p"xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Davis D.R."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Davis D.R."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Lopez-Vera E."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Lopez-Vera E."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Olivera B.M."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Olivera B.M."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Watkins M."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Watkins M."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Bulaj G."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Bulaj G."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Yoshikami D."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Yoshikami D."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Skalicky J.J."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Skalicky J.J."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Walewska A."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Walewska A."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Han T.S."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Han T.S."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Zhang M.-M."xsd:string |
| http://purl.uniprot.org/citations/18831583 | http://purl.uniprot.org/core/author | "Zhang M.-M."xsd:string |