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Approaches to Delineate Disulfide Connectivities in Pharmaceutical Peptides

  • David Wilson
  • Norelle L. Daly
Reference work entry

Abstract

Disulfide-rich peptides have been developed as treatments for diseases and disorders such as diabetes and pain, and many more are being explored for their potential in drug design. Based on this potential and the enormous diversity of these peptides in nature, particularly in venoms and plants, there is significant interest in characterizing novel disulfide-rich peptides. Elucidating the disulfide-bond connectivities is a crucial step to enable the structure-function relationships to be determined, which can assist in the development of more potent and selective analogues. NMR spectroscopy can be a very convenient and powerful tool for determining the disulfide connectivities, and being a nondestructive technique allows other analyses to be subsequently carried out. The range of NMR-based approaches that have been used include simple, comparative analyses for analogues of well-characterized peptides, determination of high-resolution structures, and measurement of scalar couplings across diselenide bonds. The use of computational Bayesian methodologies is also a promising approach for determining connectivities using cysteine-only NMR data.

Keywords

Disulfide bond Cystine knot Cyclotide Venom peptide Selenocysteine 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and MedicineJames Cook UniversityCairnsAustralia

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