**8. Acknowledgments**

260 Non-Viral Gene Therapy

Scheme 2. Synthetic strategy for peptide-phospholipid conjugates

components to assemble effective non-viral vectors.

**7. Conclusions** 

(SPDP) to form compound **4**, followed by coupling with oligopeptides, (Arg)*n*Cys (R*n*C; *n* = 5, 8). Undetachable type of analogous conjugates (DPPE-S-R*n*) were also synthesized with a coupling agent, *N*-(4-maleimidobutyroxy)succinimide (GMBS) and DPPE to form compound **5**, followed by coupling with (Arg)nCys. When the disulfide-type conjugates were applied to gene delivery assay in vitro, 3-5 times higher trasnfection activity was observed compared with the corresponding undetachable conjugates. This result suggests that such a cleavable type of peptide-phospholipid conjugate is one of promising

We described herein that PCL composed of the low-molecular-weight polyamine conjugates, DCP–spermidine (**DCP-spd**) and DCP–spermine (**DCP-spm**), exhibit much higher gene transfer activity than PEI(1800) conjugate-based **DCP-PEI**(PCL). The former compounds generate 150–400 nm diameter lipoplexes whereas the latter gives rise to large aggregates. In the case of the former compounds, AFM images clearly reveal a morphological change upon acidification, indicating DNA release from the lipoplexes, whereas, in contrast, the morphology of micellar aggregates is insensitive to pH change. A The authors thank Dr. Robert C. MacDonald for helpful comments and discussion. The present work was supported by "Grant-in-Aid for Scientific Research on Innovative Areas 2006 (Molecular Science of Fluctuations towards Biological Functions)" (201107510, 23107713) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of the Japanese Government.
