In order to prepare pyrimidine nucleoside-peptide conjugate concisely, we developed a one-pot synthetic strategy. Started from uridine, 5-S-acetyl-thiomethyl-2＇,3 ＇-di-O-isopropylidene-uridine （4） was synthesized as the key intermediate in four steps. Under acidic condition, compound 4 was deprotected and reacted with PySS-R （8, 12, 15, Py = 2-pyridyl, R = amino acid or peptide） in one pot to form uridine conjugates （9, 13, 2） with disulfide bond as linker.
Given its ability to knock down essentially any gene of interest, siRNA has been one of the promising candidates for gene therapy. However, like other nucleic-acid-based drugs, its poor cellular uptake poses a major challenge. Here we briefly summarize the use of cell penetrating peptides （CPPs） as a novel and promising approach for siRNA delivery. The main advantages of CPPs are their low toxicity and high efficiency.
