Peptides and proteins are increasingly more applicable in many fields like chemical biology, therapeutics development and material science. In particular, chemically functionalized peptides or proteins are of interest because they possess improved properties compared to their unmodified counterparts. Proteins can be constructed from the 20 canonical amino acids, which means that they possess a huge functional diversity. Therefore, chemoselective after-synthesis modifications are essential to obtain proteins with known architectures. Moreover, having a well-defined modification, not only in the type of linkage but also the number and location of the modifications, is crucial for the approval of emerging peptide/protein therapeutics. Therefore, so-called site-selective transformations are used that can not only differentiate between the grand pool of functionalities present on proteins but can also distinguish between different locations on the protein (N-terminus, in-chain, or C-terminus). In this thesis we examine how chemoselectivity can give rise to site-selectivity. We examine a novel chemoselective transformation, apply it and take it a step further to introduce site-selectivity. Inspired by in-space proximity-promoted site-selective modifications, we also sought to use a proximity effect to create amide bonds in physiological conditions, as a first step in our goal to develop an in situ drug-synthesis approach.
Katerina was born on November 13th, 1998 in Larnaka, Cyprus. She attended the Lyceum Linopetra in Limassol, from where she graduated in 2016. The same year, she joined the Bachelor’s program Molecular Life Sciences at Radboud University, with focus on chemistry, biochemistry and neuroscience. She obtained her Bachelor’s degree in 2019, when she next pursued her Master’s in Molecular Life Sciences with specialization Chemistry of Life. During her education, she gained knowledge on synthetic organic chemistry while working on new synthesis routes for double-functionalized trans-cyclooctenes, under the supervision of Kim Bonger and Dennis Löwik. For her final master thesis, Katerina joined the group of Paul Kouwer, working on the formation of hyaluronic acid immunobrushes and investigating their potential in T-cell activation. She obtained her Master’s degree in 2021. In October 2021, she joined Kevin Neumann’s group as a PhD candidate focusing on new approaches for drug delivery and activation.