Our lab aims to identify new bioorthogonal reactions for the synthesis and modification of functional peptides and proteins. We apply these highly selective organic reactions to study functional consequences of naturally occurring posttranslational protein modifications (PTMs) as well as to generate novel peptide- and protein-conjugates for pharmaceutical and medicinal applications.
In this presentation, l will focus on the delivery of synthetic protein conjugates into living cells. Here, we employ cyclic cell penetrating peptides (cCPPs) for the cytosolic protein transport.1 For protein modification we use a combined approach of intein expression as well as recently developed bioorthogonal reactions and enzymatic ligations, for instance the so-called Tub-tag labeling.2 This concept is finally applied to generate cell-permeable nanobodies,3 i.e. small antigen binding proteins that remain active within the reductive milieu inside living cells, as well as the subcellular targeting of protein conjugates.4