On Friday 1 July 2022, Ann-Kathrin Mündler will defend her PhD thesis "Synthesis and evaluation of bioconjugated peptides for the study of gastro-intestinal absorption and transport".
Time: 13.00
Place: Building 341, auditorium 22 & zoom: https://dtudk.zoom.us/meeting/register/u5Mvdu6uqDorE9H0iASpj4n_RmAMh3qWBK2A
Please be aware that the PhD defense may be recorded - This will also be informed at the beginning of the PhD defense.
Supervisor: Professor Thomas Lars Andresen
Co-Supervisor: Associate Professor Andrew Urquhart and Dr. Morten Borre Hansen
Assessment committee:
Professor Mads Hartvig Clausen, DTU Kemi
Professor Hanne Nielsen, University of Copenhagen
Professor Alberto Fernández-Tejada, CiCbioGUNE
Chairperson:
Associate Professor Paul Kempen
Abstract:
Peptides exhibit many advantageous properties. Their high potency and low systemic toxicity make them very interesting drug candidates. One way of administering peptide drugs is via the oral route. There, the drug is swallowed and absorbed by the body in the stomach or intestine. However, the intrinsic properties of peptides make this absorption process a highly challenging endeavor. Peptides are highly susceptible to enzymatic degradation and in addition often exhibit a low membrane permeability. This results in the low bioavailability of peptides, describing the extent to which the drug enters the systemic circulation. Systemic circulation is a prerequisite for the drug’s successful delivery, therefore, different ways have been developed to increase the bioavailability of oral peptide drugs. One of them describes the chemical modification of the peptide itself, thereby improving its properties, which in return results in enhancing its overall bioavailability. In this work, different ways of chemically modifying peptides to enhance their intrinsic properties were studied and developed. We show how peptide drugs interact with the components of the biological gastro-intestinal fluids, influencing their bioavailability. In addition, we show how the chemical modification stapling can positively alter these behaviors. In another approach, we study the influence of peptide lipidation on general peptide properties like solubility, membrane interactions and self-association. Thereby, we elucidate new interrelations between the different properties and shed new light on understanding the complexity of peptide lipidation. Finally, we propose a new drug delivery system for intestinal translocation based on the pH-low insertion peptide (pHLIP), providing a novel way of transporting peptide drugs across the intestinal barrier. In conclusion, we present three different ways of how the chemical modification of peptides can be utilized to enhance their properties for oral peptide delivery.
Best regards,
Charlotte