Chemical conjugation of an mRNA cap analogue with a cell-penetrating peptide as a potential membrane permeable translation inhibitor

We present a versatile method for chemical conjugation of a dinucleotide cap analogue with a cell-penetrating peptide. The final coupling reaction is between an azide-modified peptide (MPS-N3)-a fragment that is responsible for transport of the conjugate through the cell membrane, with a biologically active compound-and an alkynylated cap structure, using the Cu(I)-catalyzed click reaction.