Postdoctoral Researcher, EPFL
Phage Display Selection of Peptides that Resist Proteases in the Gastrointestinal Tract
Oral delivery of peptide or protein drugs poses one of the greatest challenges in the pharmaceutical industry that is currently hampered by the metabolic instability and/or limited intestinal uptake. In this work, we succeeded in generating small-sized (< 1500 Da) high affinity target-specific peptide ligands (Kis < 10 nM) that resist gastrointestinal (GI) proteases. We achieved this by conformationally constraining peptides with chemical bridges and by applying an in vitro evolution procedure with a built-in proteolytic selection process. Peptide orally applied to mice by gavage efficiently resisted proteases in all regions of the GI tract. More than 30% of the applied peptide remained intact and small quantities reached the blood stream. The strategy is the first one that allowed generating target-tailored peptide ligands remaining active in the GI tract, and presents a promising path to generating oral peptide drugs.
Xu-Dong Kong studied biochemical engineering and protein crystallography under the supervision of Prof. Jian-He Xu at East China University of Science and Technology (China) and Prof. Jiahai Zhou at Shanghai Institute of Organic Chemistry (China) during his Ph.D. He joined Prof. Christian Heinis’ research group at EPFL as a postdoctoral researcher in 2015. Currently, his research focuses on the development of orally available double-bridged peptide therapeutics by phage display.