Click SynB3 – Click Peptides

SynB3 is a cell-penetrating peptide (CPP) with high efficacy at crossing the cell membrane with no significant toxicity. SynB3, like other CPPs, can cross the blood-brain barrier (BBB). Although the mode of crossing remains unclear, synB3 has been conjugated to a few cargoes and shown to be adequately present in the brain. Synb3 provides promise for the delivery of antisense oligonucleotides as therapy for conditions such as Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). The treatment of these conditions has been hampered by the lack of cargo delivery methods that can be tissue-specific and cross the BBB. SynB3 in mouse models was shown to be an effective method of delivering therapeutics across the BBB for SMA treatment. SynB3 is labelled at the N-terminus with an alkyne attachment for ease of reaction with an opposite Click reactive partner (azide). Azide-alkyne cycloaddition has become the most popular Click reaction. Alkyne-synB3 allows various applications, particularly for protein conjugation, modification, and drug delivery.