UNASSIGNED: Animal venoms and toxins are a valuable source of bioactive peptides with pharmacologic relevance as potential drug leads. A large subset of biologically active peptides discovered up till now contain @entity1520 bridges that enhance stability and activity. To discover new members of this class of peptides, we developed a workflow screening specifically for those peptides that contain inter- and intra-molecular @entity1520 bonds by means of three-dimensional (3D) mass mapping. Two intrinsic properties of the @entity599 atom, (1) its relatively large negative mass defect, and (2) its isotopic composition, allow for differentiation between @entity462 -containing peptides and peptides lacking @entity599 . High @entity599 content in a peptide decreases the normalized @entity5547 ( @entity5547 ) and increases the normalized isotopic shift (NIS). Hence in a 3D plot of mass, NIS, and @entity5547 , peptides with @entity599 appear in this plot with a distinct spatial localization compared with peptides that lack @entity599 . In this study we investigated the skin secretion of two frog species; Odorrana schmackeri and @entity69797 . Peptides from the crude skin secretions were separated by nanoflow LC, and of all eluting peptides high resolution zoom scans were acquired in order to accurately determine both monoisotopic mass and average mass. Both the @entity5547 and the NIS were calculated from the experimental data using an in-house developed MATLAB script. Candidate peptides exhibiting a low @entity5547 and high NIS values were selected for targeted de novo sequencing, and this resulted in the identification of several novel inter- and intra-molecular @entity1520 bond containing peptides. Graphical Abstract    .

Screening Method for the Discovery of Potential Bioactive XXXX -Containing Peptides Using 3D Mass Mapping.

@entity462 :: ('MESH:D003545', 'Chemical') :: ['cysteine'] @entity69797 :: ('8348', 'Species') :: ['Bombina variegata'] @entity1520 :: ('CHEBI:48343', 'Chemical') :: ['disulfide'] @entity599 :: ('MESH:D013455', 'Chemical') :: ['sulfur'] @entity5547 :: ('MESH:D000849', 'Disease') :: ['nominal mass defect', 'NMD']
@entity462 :: (MESH:D003545,Chemical) :: ['Cysteine']
