Anthracene readily forms photoadducts, anthracene dimers, and this photodimerization reaction has been well characterized. In general, however, the reaction requires close proximity and certain spatial alignment of both reaction partners. DNA could provide an ideal scaffold for accelerating the photocyclic addition. We synthesized a number of anthracene-DNA conjugates. The sequences of the conjugates, 5'AntODNn and 3'AntODNn (the length of methylene linkers: n = 3 or 6), were designed to bind adjacent sequences of the template with the anthracene units directed such that they stacked with each other. The conjugates were only dimerized in the presence of the template by light irradiation. The efficiency was affected by one-base displacement in the template sequence.
The formation of Fc-fusions, in which biologically active molecules and the Fc fragment of antibodies are linked to each other, is one of the most efficient and successful half-life extension technologies to be developed and applied to peptide and protein pharmaceuticals thus far. Fcfusion compounds are generally produced by recombinant methods. However, these cannot be applied to artificial middle molecules, such as peptides with non-natural amino acids, unnatural cyclic peptides, or pharmaceutical oligonucleotides. Here, we developed a simple, efficient, semisynthetic method for Fc-fusion production involving our previously developed enzymatic N-terminal extension reaction (i.e., NEXT-A reaction) and strain-promoted azide−alkyne cycloaddition, achieving quantitative conversion and high selectivity for the N-terminus of the Fc protein. An Fc-fusion compound prepared by this method showed comparable biological activity to that of the original peptide and a long-circulating plasma half-life. Thus, the proposed method is potentially applicable for the conjugation of a wide range of pharmaceutical components.
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