Screening, large-scale production and structure-based classification of cystine-dense peptides.

摘要: 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 expense of chemical synthesis. We developed reliable biological methods for high-throughput expression, screening large-scale production these peptides: 46 were successfully produced in multimilligram quantities, >600 more deemed expressible stringent criteria. Many showed resistance to temperature, proteolysis and/or reduction, all displayed inhibitory activity against at least 1 20 ion channels tested, thus confirming functionality. Crystal structures 12 confirmed proper cystine topology utility crystallography study molecules but also highlighted need rational classification. Previous categorization attempts have focused on subsets featuring distinct motifs. Here we present a global definition, classification analysis >700 cystine-dense peptides, providing unifying framework molecules.