6av8

Publication Abstract from PubMed

Peptides folded through interwoven disulfides display extreme biochemical properties and unique medicinal potential. However, their exploitation has been hampered by the limited amounts isolatable from natural sources and the expense of chemical synthesis. We developed reliable biological methods for high-throughput expression, screening and large-scale production of these peptides: 46 were successfully produced in multimilligram quantities, and >600 more were deemed expressible through stringent screening criteria. Many showed extreme resistance to temperature, proteolysis and/or reduction, and all displayed inhibitory activity against at least 1 of 20 ion channels tested, thus confirming their biological functionality. Crystal structures of 12 confirmed proper cystine topology and the utility of crystallography to study these molecules but also highlighted the need for rational classification. Previous categorization attempts have focused on limited subsets featuring distinct motifs. Here we present a global definition, classification and analysis of >700 structures of cystine-dense peptides, providing a unifying framework for these molecules.

Screening, large-scale production and structure-based classification of cystine-dense peptides.,Correnti CE, Gewe MM, Mehlin C, Bandaranayake AD, Johnsen WA, Rupert PB, Brusniak MY, Clarke M, Burke SE, De Van Der Schueren W, Pilat K, Turnbaugh SM, May D, Watson A, Chan MK, Bahl CD, Olson JM, Strong RK Nat Struct Mol Biol. 2018 Mar;25(3):270-278. doi: 10.1038/s41594-018-0033-9. Epub, 2018 Feb 26. PMID:29483648^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.