Delivery of steric block morpholino oligomers by (R-X-R)(4) peptides: structure–activity studies

Abes, Rachida; Moulton, Hong M.; Clair, Philippe; Yang, Sung-Tae; Abes, Said; Melikov, Kamran; Prevot, Paul; Youngblood, Derek S.; Iversen, Patrick L.; Chernomordik, Leonid V.; Lebleu, Bernard

Some compounds in this series (11 in Figure 2A ) have hydrophobicities comparable to the parent (R-Ahx-R) 4 -PMO (compound 5) taken as a reference while others (compounds 8-10) have a significantly higher hydrophobicity, as monitored by C18-column chromatography ( Figure 2B ). These conjugates were analyzed for splicing correction efficiency at various concentrations ( Figure 2C and data not shown). Splicing correction efficiency is lower for the more hydrophobic conjugates (compounds 8-10) and remains the most active for compound 5. As expected, compounds 8-11 had similar affinities for heparin ( Figure 2D ). Therefore, differences in splicing correction in this series were largely influenced by hydrophobicity. We cannot explain why compound 11 has a lower splicing correction activity than compound 5 as their hydrophobicity and heparin affinity are similar.