Discovery and application of cysteine-rich peptides from medicinal plants in drug development

Cysteine-rich peptides (CRPs) are mini-proteins, highly diverse in sequence and possess great thermal and enzymatic stability. They can be exploited as scaffolds for engineering peptidyl drugs. The focus of my thesis is to isolate and characterize CRPs from Jasminum sambac of Oleaceae family. Using a peptidomic approach we have identified 15 jasmintides with a novel disulfide connectivity of CysI-CysV, CysII-CysIV and CysIII-CysVI. The discovery of a new CRP family expands our knowledge of cystine motifs in plant CRPs. Understanding the structure and stability of jasmintides could lead to their use as a scaffold for designing peptide drugs. My thesis also describes the application of a CRP as a scaffold by grafting substance P antagonists into sunflower trypsin inhibitor-1. The grafted analogs are bifunctional and showed improved stability against endo- and exopeptidases. Taken together, my thesis demonstrates that CRPs could be useful for developing peptide therapeutics.​Doctor of Philosophy (SBS