Development of a general methodology for labelling peptide-morpholino oligonucleotide conjugates using alkyne-azide click chemistry

We describe a general methodology for fluorescent labelling of peptide conjugates of phosphorodiamidate morpholino oligonucleotides (PMO) by alkyne functionalizion of peptides, subsequent conjugation to PMO and labelling with a fluorescent compound (Cy5-azide). Two peptide-PMO (PPMO) examples are shown. No detrimental effect was seen of such labelled PMO in a biological assay.