Synthesis of Photoswitchable Homodimeric Polypeptides: Towards Biological Applications

摘要

Homodimeric polypeptides have been largely investigated on account of their enhanced properties, such as gene delivery and selective targeting, as compared to the unmodified neptides [1.2]. Dimer formation is generally achieved through cysteine bridges derived from monomer oxidation, which can be very problematic in the presence of more than one cvsteine residue in a sequence. Herein, we report the synthesis of photoswitchable homodimeric polypeptides by the incorporation of an anthracene moiety. Photochemical reactions have found widespread use in the biological sciences since they are characterized bv spatial and temporal control, and a short reaction time. Classic [4+4]-ene nhotodimerization reactions such as that exhibited by anthracene dimerization, have been successfully applied to sensing applications, biomolecule-ligations and the formation of hvdrogels [3,4]. Experimental work on the rate enhancement of the [4+4]-photodimenzation of anthracene through non covalent host-guest complex formation in the presence of the macrocytic host cucurbit[8]uril (CB[8]) [5] has already been carried out in the Scherman sroup CB[8], which can accommodate two guests simultaneously in its large hydrophobic cavity brings together two anthracene moieties in a face-to-face π-π-stacked arrangement, which results in a much faster photochemical dimerization than in the absence of the host molecule. The use of a supramolecular approach will allow us to obtain a stable nhotoswicthable homodimer, covalently bound at a precise point, avoiding any synthetic doubt raised by the presence of more cysteine residues in a peptide sequence.