Xiaolin Dai, Diana M. Mate, Ulrich Glebe, Tayebeh Mirzaei Garakani, Andrea Körner, Ulrich Schwaneberg, Alexander Böker

• Sortase A (SrtA) from Staphylococcus aureus has been often used for ligating a protein with other natural or synthetic compounds in recent years. Here we show that SrtA-mediated ligation (SML) is universally applicable for the linkage of two purely artificial building blocks. Silica nanoparticles (NPs), poly(ethylene glycol) and poly(N-isopropyl acrylamide) are chosen as synthetic building blocks. As a proof of concept, NP-polymer, NP-NP, and polymer-polymer structures are formed by SrtA catalysis. Therefore, the building blocks are equipped with the recognition sequence needed for SrtA reaction-the conserved peptide LPETG-and a pentaglycine motif. The successful formation of the reaction products is shown by means of transmission electron microscopy (TEM), matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-ToF MS), and dynamic light scattering (DLS). The sortase catalyzed linkage of artificial building blocks sets the stage for the development of a new approach to link synthetic structures in casesSortase A (SrtA) from Staphylococcus aureus has been often used for ligating a protein with other natural or synthetic compounds in recent years. Here we show that SrtA-mediated ligation (SML) is universally applicable for the linkage of two purely artificial building blocks. Silica nanoparticles (NPs), poly(ethylene glycol) and poly(N-isopropyl acrylamide) are chosen as synthetic building blocks. As a proof of concept, NP-polymer, NP-NP, and polymer-polymer structures are formed by SrtA catalysis. Therefore, the building blocks are equipped with the recognition sequence needed for SrtA reaction-the conserved peptide LPETG-and a pentaglycine motif. The successful formation of the reaction products is shown by means of transmission electron microscopy (TEM), matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-ToF MS), and dynamic light scattering (DLS). The sortase catalyzed linkage of artificial building blocks sets the stage for the development of a new approach to link synthetic structures in cases where their synthesis by established chemical methods is complicated.…