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Conformational μConotoxin PIIIA Isomers Revisited: Impact of Cysteine Pairing on Disulfide-Bond Assignment and Structure Elucidation.

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Title: Conformational μConotoxin PIIIA Isomers Revisited: Impact of Cysteine Pairing on Disulfide-Bond Assignment and Structure Elucidation.
Authors: Heimer, Pascal1, Tietze, Alesia A.2, Bäuml, Charlotte A.1, Resemann, Anja3, Mayer, Franz Josef3, Suckau, Detlev3, Ohlenschläger, Oliver4, Tietze, Daniel5 tietze@chemie.tu-darmstadt.de, Imhof, Diana1 dimhof@uni-bonn.de
Source: Analytical Chemistry. 3/6/2018, Vol. 90 Issue 5, p3321-3327. 7p.
Subjects: Conformational isomerism, Peptide synthesis, Disulfides synthesis, Cysteine, Nuclear magnetic resonance spectroscopy, Chemical synthesis
Abstract: Peptides and proteins carrying high numbers of cysteines can adopt various 3D structures depending on their disulfide connectivities. The unambiguous verification of such conformational isomers with more than two disulfide bonds is extremely challenging, and experimental strategies for their unequivocal structural analysis are largely lacking. We synthesized all 15 possible isomers of the 22mer conopeptide μPIIIA and applied 2D NMR spectroscopy and MS/MS for the elucidation of its structure. This study provides intriguing insights in how the disulfide connectivity alters the global fold of a toxin. We also show that analysis procedures involving comprehensive combinations of conventional methods are required for the unambiguous assignment of disulfides in cysteine-rich peptides and proteins and that standard compounds are crucially needed for the structural analysis of such complex molecules. [ABSTRACT FROM AUTHOR]
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Database: Engineering Source
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Abstract:Peptides and proteins carrying high numbers of cysteines can adopt various 3D structures depending on their disulfide connectivities. The unambiguous verification of such conformational isomers with more than two disulfide bonds is extremely challenging, and experimental strategies for their unequivocal structural analysis are largely lacking. We synthesized all 15 possible isomers of the 22mer conopeptide μPIIIA and applied 2D NMR spectroscopy and MS/MS for the elucidation of its structure. This study provides intriguing insights in how the disulfide connectivity alters the global fold of a toxin. We also show that analysis procedures involving comprehensive combinations of conventional methods are required for the unambiguous assignment of disulfides in cysteine-rich peptides and proteins and that standard compounds are crucially needed for the structural analysis of such complex molecules. [ABSTRACT FROM AUTHOR]
ISSN:00032700
DOI:10.1021/acs.analchem.7b04854