Abstract

Cyclic Peptides from Plants: An Inspiration for Drug Discovery

Seetharama Jois, Professor, University of Louisiana

Plant-derived cyclic peptides, or mini-proteins that have a multicyclic structure with disulfide bonds, are resistant to thermal, chemical, and enzymatic degradation, and are orally bioavailable. These multicyclic peptides do not present any immunogenicity and are amenable to sequence modification. We have grafted the peptides that inhibit the protein-protein interaction and have therapeutic applications for immunomodulation and cancer onto sunflower trypsin inhibitor (SFTI) peptide template. These grafted peptides inhibit the CD2-CD58 interaction in cell adhesion assays at nanomolar concentrations. The newly designed molecules exhibit in vivo stability and immunomodulation function by inhibiting adhesion between CD2-CD58. The grafted peptides also inhibit the interactions of EGFR that have important implications in breast and lung cancer. Circular dichroism and mass spectrometry data of peptides at different temperatures in solution suggested that these cyclic peptides are stable at high temperature. Stability studies in serum using HPLC method indicated that peptides were stable in serum for nearly 48 hrs. Such molecules present a novel way of treating autoimmune disease and cancer compared to existing biologics. This research was supported by funding from Louisiana Campuses Research Initiative (LaCRI) and by funding from NCI/NIH (R15 CA188225-01A1).