Strategies for the Preparation of Synthetic Transfection Vectors

  • Asier Unciti-BrocetaEmail author
  • Matthew N. Bacon
  • Mark Bradley
Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 296)



In the late 1980s independent work by Felgner and Behr pioneered the use of cationic materials to complex and deliver nucleic acids into eukaryotic cells. Since this time, a vast number of synthetic transfection vectors, which are typically divided into two main “transfectors”, have been developed namely: (1) cationic lipids and (2) polycationic polymers. In this chapter the main synthetic approaches used for the synthesis of these compounds will be reviewed with particular attention paid to: cationic lipids and dendrimers. This review is aimed primarily at the younger audience of doctoral students and non-specialist readers.

Graphical Abstract


Cationic lipids Cell delivery Dendrimers Gene therapy Transfection 



Acquired immune deficiency syndrome


10,10′-bis[3-carboxypropyl]-9,9′-biacridinium dinitrate


Bisguanidinium tren-cholesterol




















Dioctadylamidoglycylspermine, trifluoroacetic salt




N-[1-(2,3-Dioleoyloxy)propyl-N-[1-(2-hydroxy)ethyl]-N,N-dimethylammonium iodide


1,2-Dioleyloxypropyl-3-dimethylhydroxyethylammonium bromide


N,N-Dimethyl-N-[2-sperminecarboxamido)-ethyl]-2,3-bis(dioleyl oxy)-1-propanimium pentachloride


N-[1-(2,3-Dioleyloxy)propyl]-N,N,N-trimethylammonium chloride




Gemini Surfactant 1




















Synthetic Amphiphiles INTerdisciplinary


Small interfering RNA


N-[Tris(3-(amino)propyl)methyl]tetraeicosanamide trihydrochloride


Trifluoroacetic acid




Triisopropyl silane





We thank the MRC and BBSRC for funding.


  1. 1.
    Gaur RK, Rossi JJ (2009) Regulation of gene expression by small RNAs. CRC, Taylor & Francis, Boca Raton, p 431CrossRefGoogle Scholar
  2. 2.
    Fu J-D, Jung Y, Chan CW, Li RA (2008) Stem Cells Dev 17:315PubMedCrossRefGoogle Scholar
  3. 3.
    Okita K, Ichisaka T, Yamanaka S (2007) Nature 446:313CrossRefGoogle Scholar
  4. 4.
    Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Cell 131:861PubMedCrossRefGoogle Scholar
  5. 5.
    Taira K, Kataoka K, Niidome T (eds) (2005) Non-viral gene therapy: gene design and delivery. Springer, TokyoGoogle Scholar
  6. 6.
    Templeton NS (ed) (2008) Gene and cell therapy: therapeutic mechanisms and strategies. Marcel Dekker, New YorkGoogle Scholar
  7. 7.
    Conwell CC, Huang L (2005) In: Taira K, Kataoka K, Niidome T (eds) Non-viral gene therapy: gene design and delivery. Springer, Tokyo, p 3CrossRefGoogle Scholar
  8. 8.
    Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, Viswanathan A, Holder GE, Stockman A, Tyler N, Petersen-Jones S, Bhattacharya SS, Thrasher AJ, Fitzke FW, Carter BJ, Rubin GS, Moore AT, Ali RR (2008) N Engl J Med 358:2231PubMedCrossRefGoogle Scholar
  9. 9.
    Excoffon KJDA, Koerber JT, Dickey DD, Murtha M, Keshavjee S, Kaspar BK, Zabner J, Schaffer DV (2009) Proc Natl Acad Sci USA 106:3865PubMedCrossRefGoogle Scholar
  10. 10.
    Mitsuyasu RT, Merigan TC, Carr A, Zack JA, Winters MA, Workman C, Block M, Lalezari J, Becker S, Thornton L, Akil B, Khanlou H, Finlayson R, McFarlane R, Smith DE, Garsia R, Ma D, Law M, Murray JM, Von Kalle C, Ely JA, Patino SM, Knop AE, Wong P, Todd AV, Haughton M, Furey C, Macpherson JL, Symonds GP, Evans LA, Pond SM, Cooper DA (2009) Nat Medicine 15:285CrossRefGoogle Scholar
  11. 11.
    Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massague J (2008) Nature 451:147PubMedCrossRefGoogle Scholar
  12. 12.
    List of current clinical trials can be found at
  13. 13.
    Yang F, Cho S-W, Son SM, Bogatyrev SR, Singh D, Green JJ, Mei Y, Park S, Bhang SH, Kim B-S, Langer R, Anderson DG (2010) Proc Natl Acad Sci USA 107:3317Google Scholar
  14. 14.
    Hoag H (2005) Nature 435:530PubMedCrossRefGoogle Scholar
  15. 15.
    Machida CA (ed) (2002) Viral vectors for gene therapy: methods and protocols. Humana Press, TotowaGoogle Scholar
  16. 16.
    Young LS, Searle PF, Onion D, Mautner V (2006) J Pathol 208:299PubMedCrossRefGoogle Scholar
  17. 17.
    Azzam T, Domb AJ (2004) Curr Drug Deliv 1:165PubMedCrossRefGoogle Scholar
  18. 18.
    Ma H, Diamond SL (2001) Curr Pharm Biotechnol 2:1PubMedCrossRefGoogle Scholar
  19. 19.
    Mehier-Humbert S, Guy RH (2005) Adv Drug Deliv Rev 57:733PubMedCrossRefGoogle Scholar
  20. 20.
    Villemejane J, Mir LM (2009) Br J Pharmacol 157:207PubMedCrossRefGoogle Scholar
  21. 21.
    Check E (2005) Nature 434:812PubMedCrossRefGoogle Scholar
  22. 22.
    Scott DW (2006) Blood 108:2CrossRefGoogle Scholar
  23. 23.
    Hacein-Bey-Abina S, von Kalle C, Schmidt M, Le Deist F, Wulffraat N, McIntyre E, Radford I, Villeval JL, Fraser CC, Cavazzana-Calvo M, Fischer A (2003) N Engl J Med 348:255PubMedCrossRefGoogle Scholar
  24. 24.
    Woods NB, Bottero V, Schmidt M, von Kalle C, Verma IM (2006) Nature 440:1123PubMedCrossRefGoogle Scholar
  25. 25.
    Li S, Huang L (2000) Gene Ther 7:31PubMedCrossRefGoogle Scholar
  26. 26.
    Miller AD (2003) Curr Med Chem 10:1195PubMedCrossRefGoogle Scholar
  27. 27.
    Dass CR (2004) J Mol Med 82:579PubMedCrossRefGoogle Scholar
  28. 28.
    Wagner E (2004) Pharm Res 21:8PubMedCrossRefGoogle Scholar
  29. 29.
    Walker GF, Fella C, Pelisek J, Fahrmeir J, Boeckle S, Ogris M, Wagner E (2005) Mol Ther 11:418PubMedCrossRefGoogle Scholar
  30. 30.
    Koltover I, Salditt T, Radler JO, Safinya CR (1998) Science 281:78PubMedCrossRefGoogle Scholar
  31. 31.
    van der Woude I, Visser HW, ter Beest MB, Wagenaar A, Ruiters MH, Engberts JB, Hoekstra D (1995) Biochim Biophys Acta 1240:34PubMedCrossRefGoogle Scholar
  32. 32.
    Zuhorn IS, Bakowsky U, Polushkin E, Visser WH, Stuart MCA, Engberts JBFN, Hoekstra D (2005) Mol Ther 11:801PubMedCrossRefGoogle Scholar
  33. 33.
    Behr J-P (1997) Chimia 51:34Google Scholar
  34. 34.
    Unciti-Broceta A, Díaz-Mochón JJ, Mizomoto H, Bradley M (2008) J Comb Chem 10:179PubMedCrossRefGoogle Scholar
  35. 35.
    Niculescu-Duvaz D, Heyes J, Springer CJ (2003) Curr Med Chem 10:1233PubMedCrossRefGoogle Scholar
  36. 36.
    Martin B, Sainlos M, Aissaoui A, Oudrhiri N, Hauchecorne M, Vigneron J-P, Lehn J-M, Lehn P (2005) Curr Pharm Des 11:375PubMedCrossRefGoogle Scholar
  37. 37.
    Bhattacharya S, Bajaj A (2009) Chem Commun 31:4632CrossRefGoogle Scholar
  38. 38.
    Guillot-Nieckowski M, Eisler S, Diederich F (2007) New J Chem 31:1111CrossRefGoogle Scholar
  39. 39.
    Mintzer MA, Simanek EE (2009) Chem Rev 109:259PubMedCrossRefGoogle Scholar
  40. 40.
    Hwang SJ, Davis ME (2001) Curr Opin Mol Ther 3:183PubMedGoogle Scholar
  41. 41.
    Hirko A, Tang F, Hughes JA (2003) Curr Med Chem 10:1185PubMedCrossRefGoogle Scholar
  42. 42.
    Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielsen M (1987) Proc Natl Acad Sci USA 84:7413PubMedCrossRefGoogle Scholar
  43. 43.
    Xu Y, Szoka FC Jr (1996) Biochemistry 35:5616PubMedCrossRefGoogle Scholar
  44. 44.
    Zelphati O, Szoka FC Jr (1996) Proc Natl Acad Sci USA 93:11493PubMedCrossRefGoogle Scholar
  45. 45.
    Lechardeur D, Verkman AS, Lukacs GL (2005) Adv Drug Deliv Rev 57:755PubMedCrossRefGoogle Scholar
  46. 46.
    Nicolazzi C, Garinot M, Mignet N, Scherman D, Bessodes M (2003) Curr Med Chem 10:1263PubMedCrossRefGoogle Scholar
  47. 47.
    Miller A (1998) Angew Chem 41:1768Google Scholar
  48. 48.
    Ewert K, Slack NL, Ahmad A, Evans HM, Lin AJ, Samuel CE, Safinya CR (2004) Curr Med Chem 11:133PubMedCrossRefGoogle Scholar
  49. 49.
    Tranchant I, Thompson B, Nicolazzi C, Mignet N, Scherman D (2004) J Gene Med Suppl 1:S24CrossRefGoogle Scholar
  50. 50.
    Smyth-Templeton N (2003) Curr Med Chem 10:1279PubMedCrossRefGoogle Scholar
  51. 51.
    Zuhorn IS, Engberts JB, Hoekstra D (2007) Eur Biophys J 36:349PubMedCrossRefGoogle Scholar
  52. 52.
    Tresset G (2009) PMC Biophys 2:3PubMedCrossRefGoogle Scholar
  53. 53.
    Hoekstra D, Rejman J, Wasungu L, Shi F, Zuhorn I (2007) Biochem Soc Trans 35:68PubMedCrossRefGoogle Scholar
  54. 54.
    Hofland HE, Shephard L, Sullivan SM (1996) Proc Natl Acad Sci USA 93:7305PubMedCrossRefGoogle Scholar
  55. 55.
    Resina S, Prevot P, Thierry AR (2009) PLoS One 4:e6058PubMedCrossRefGoogle Scholar
  56. 56.
    Ma B, Zhang S, Jiang H, Zhao B, Lv H (2007) J Control Release 123:184PubMedCrossRefGoogle Scholar
  57. 57.
    Pedroso de Lima MC, Neves S, Filipe A, Düzgüneş N, Simões S (2003) Curr Med Chem 10:1221PubMedCrossRefGoogle Scholar
  58. 58.
    Koynova R, Wang L, MacDonald RC (2006) Proc Natl Acad Sci USA 103:14373PubMedCrossRefGoogle Scholar
  59. 59.
    Lv H, Zhang S, Wang B, Cui S, Yan J (2006) J Control Release 14:100CrossRefGoogle Scholar
  60. 60.
    Niculescu-Duvaz D (2003) Heyes J. Springer C Curr Med Chem 10:1233CrossRefGoogle Scholar
  61. 61.
    Montier T, Benvegnu T, Jaffrès PA, Yaouanc JJ, Lehn P (2008) Curr Gene Ther 8:296PubMedCrossRefGoogle Scholar
  62. 62.
    Gardner RA, Belting M, Svensson K, Phanstiel O 4th (2007) J Med Chem 50:308PubMedCrossRefGoogle Scholar
  63. 63.
    Byk G, Dubertret C, Escriou V, Frederic M, Jaslin G, Rangara R, Pitard B, Crouzet J, Wils P, Schwartz B, Scherman D (1998) J Med Chem 41:229PubMedCrossRefGoogle Scholar
  64. 64.
    Bajaj A, Paul B, Kondaiah P, Bhattacharya S (2008) Bioconjug Chem 19:1283PubMedCrossRefGoogle Scholar
  65. 65.
    Ilies MA, Seitz WA, Johnson BH, Ezell EL, Miller AL, Thompson EB, Balaban AT (2006) J Med Chem 49:3872PubMedCrossRefGoogle Scholar
  66. 66.
    Karmali PP, Kumar VV, Chaudhuri A (2004) J Med Chem 47:2123PubMedCrossRefGoogle Scholar
  67. 67.
    Unciti-Broceta A, Holder E, Jones LJ, Stevenson B, Turner AR, Porteous DJ, Boyd AC, Bradley M (2008) J Med Chem 51:4076PubMedCrossRefGoogle Scholar
  68. 68.
    Gao X, Huang L (1991) Biochem Biophys Res Commun 79:280CrossRefGoogle Scholar
  69. 69.
    Behr JP, Demeneix B, Loeffler JP, Perez-Mutul J (1989) Proc Natl Acad Sci USA 86:6982PubMedCrossRefGoogle Scholar
  70. 70.
    Stamatatos L, Leventis R, Zuckermann MJ, Silvius JR (1988) Biochemistry 27:3917PubMedCrossRefGoogle Scholar
  71. 71.
    Felgner JH, Kumar R, Sridhar CN, Wheeler CJ, Tsai YJ, Border R, Ramsey P, Martin M, Felgner PL (1994) J Biol Chem 269:2550PubMedGoogle Scholar
  72. 72.
    Islam RU, Hean J, van Otterlo WA, de Koning CB, Arbuthnot P (2009) Bioorg Med Chem Lett 19:100PubMedCrossRefGoogle Scholar
  73. 73.
    Vigneron JP, Oudrhiri N, Fauquet M, Vergely L, Bradley JC, Basseville M, Lehn P, Lehn JM (1996) Proc Natl Acad Sci USA 93:9682PubMedCrossRefGoogle Scholar
  74. 74.
    Lebreton S, Newcombe N, Bradley M (2002) Tetrahedron Lett 43:2475CrossRefGoogle Scholar
  75. 75.
    Guénin E, Hervé AC, Floch VV, Loisel S, Yaouanc JJ, Clément JC, Férec C, Des Abbayes H (2000) Angew Chem Int Ed Engl 39:629PubMedCrossRefGoogle Scholar
  76. 76.
    Floch V, Loisel S, Guenin E, Hervé AC, Clément JC, Yaouanc JJ, Des Abbayes H, Férec C (2000) J Med Chem 43:4617PubMedCrossRefGoogle Scholar
  77. 77.
    Fletcher S, Ahmad A, Perouzel E, Heron A, Miller AD, Jorgensen MR (2006) J Med Chem 49:349PubMedCrossRefGoogle Scholar
  78. 78.
    Mahidhar YV, Rajesh M, Chaudhuri A (2004) J Med Chem 47:3938PubMedCrossRefGoogle Scholar
  79. 79.
    Bhattacharya S, Dileep PV (2004) Bioconjug Chem 15:508PubMedCrossRefGoogle Scholar
  80. 80.
    Ghosh YK, Visweswariah SS, Bhattacharya S (2002) Bioconjug Chem 13:378PubMedCrossRefGoogle Scholar
  81. 81.
    Mukherjee K, Bhattacharyya J, Sen J, Sistla R, Chaudhuri A (2008) J Med Chem 51:1967PubMedCrossRefGoogle Scholar
  82. 82.
    Wheeler CJ, Felgner PL, Tsai YJ, Marshall J, Sukhu L, Doh SG, Hartikka J, Nietupski J, Manthorpe M, Nichols M, Plewe M, Liang X, Norman J, Smith A, Cheng SH (1996) Proc Natl Acad Sci USA 93:11454PubMedCrossRefGoogle Scholar
  83. 83.
    Picquet E, Le Ny K, Delépine P, Montier T, Yaouanc JJ, Cartier D, Des Abbayes H, Férec C, Clément JC (2005) Bioconjug Chem 16:1051PubMedCrossRefGoogle Scholar
  84. 84.
    Mével M, Montier T, Lamarche F, Delépine P, Le Gall T, Yaouanc JJ, Jaffrès PA, Cartier D, Lehn P, Clément JC (2007) Bioconjug Chem 18:1604PubMedCrossRefGoogle Scholar
  85. 85.
    Paulekuhn GS, Dressman JB, Saal C (2007) J Med Chem 50:6665PubMedCrossRefGoogle Scholar
  86. 86.
    Aberle AM, Bennett MJ, Malone RW, Nantz MH (1996) Biochim Biophys Acta 1299:281PubMedCrossRefGoogle Scholar
  87. 87.
    Gebeyehu G, Jessee JA, Ciccarone VC, Hawley-Nelson P, Chytil A (1994) US Patent 5(334):761Google Scholar
  88. 88.
    Cooper RG, Etheridge CJ, Stewart L, Marshall J, Rudginsky S, Cheng SH, Miller AD (1998) Chem Eur J 4:137CrossRefGoogle Scholar
  89. 89.
    Lee ER, Marshall J, Siegel CS, Jiang C, Yew NS, Nichols MR, Nietupski JB, Ziegler RJ, Lane MB, Wang KX, Wan NC, Scheule RK, Harris DJ, Smith AE, Cheng SH (1996) Hum Gene Ther 7:1701PubMedCrossRefGoogle Scholar
  90. 90.
    Ewert K, Ahmad A, Evans HM, Schmidt HW, Safinya CR (2002) J Med Chem 45:5023PubMedCrossRefGoogle Scholar
  91. 91.
    Remy J-S, Sirlin C, Vierling P, Behr JP (1994) Bioconjug Chem 5:647PubMedCrossRefGoogle Scholar
  92. 92.
    Ewert KK, Evans HM, Bouxsein NF, Safinya CR (2006) Bioconjug Chem 17:877PubMedCrossRefGoogle Scholar
  93. 93.
    Ronsin G, Perrin C, Guédat P, Kremer A, Camilleri P, Kirby AJ (2001) Chem Commun 21:2234CrossRefGoogle Scholar
  94. 94.
    Sen J, Chaudhuri A (2005) J Med Chem 48:812PubMedCrossRefGoogle Scholar
  95. 95.
    Patel M, Vivien E, Hauchecorne M, Oudrhiri N, Ramasawmy R, Vigneron JP, Lehn P, Lehn JM (2001) Biochem Biophys Res Commun 281:536PubMedCrossRefGoogle Scholar
  96. 96.
    Bajaj A, Mishra SK, Kondaiah P, Bhattacharya S (2008) Biochim Biophys Acta 1778:1222PubMedCrossRefGoogle Scholar
  97. 97.
    Oudrhiri N, Vigneron JP, Peuchmaur M, Leclerc T, Lehn JM, Lehn P (1997) Proc Natl Acad Sci USA 94:1651PubMedCrossRefGoogle Scholar
  98. 98.
    Luton D, Oudrhiri N, de Lagausie P, Aissaoui A, Hauchecorne M, Julia S, Oury JF, Aigrain Y, Peuchmaur M, Vigneron JP, Lehn JM, Lehn P (2004) J Gene Med 6:328PubMedCrossRefGoogle Scholar
  99. 99.
    Rothbard JB, Jessop TC, Lewis RS, Murray BA, Wender PA (2004) J Am Chem Soc 126:9506PubMedCrossRefGoogle Scholar
  100. 100.
    Heyes JA, Niculescu-Duvaz D, Cooper RG, Springer CJ (2002) J Med Chem 45:99PubMedCrossRefGoogle Scholar
  101. 101.
    Sochanik A, Kaida I, Mitrus I, Rajca A, Szala S (2000) Cancer Gene Ther 7:513PubMedCrossRefGoogle Scholar
  102. 102.
    Desigaux L, Sainlos M, Lambert O, Chevre R, Letrou-Bonneval E, Vigneron JP, Lehn P, Lehn JM, Pitard B (2007) Proc Natl Acad Sci USA 104:16534PubMedCrossRefGoogle Scholar
  103. 103.
    Tang F, Hughes JA (1999) J Control Release 62:345PubMedCrossRefGoogle Scholar
  104. 104.
    Kirby AJ, Camilleri P, Engberts JB, Feiters MC, Nolte RJ, Söderman O, Bergsma M, Bell PC, Fielden ML, García Rodríguez CL, Guédat P, Kremer A, McGregor C, Perrin C, Ronsin G, Van Eijk MC (2003) Angew Chem Int Ed 42:1448CrossRefGoogle Scholar
  105. 105.
    Bombelli C, Giansanti L, Luciani P, Mancini G (2009) Curr Med Chem 16:171PubMedCrossRefGoogle Scholar
  106. 106.
    Bajaj A, Kondaiah P, Bhattacharya S (2007) Bioconjug Chem 18:1537PubMedCrossRefGoogle Scholar
  107. 107.
    Bajaj A, Kondiah P, Bhattacharya S (2007) J Med Chem 50:2432PubMedCrossRefGoogle Scholar
  108. 108.
    Wasungu L, Scarzello M, van Dam G, Molema G, Wagenaar A, Engberts JB, Hoekstra D (2006) J Mol Med 84:774PubMedCrossRefGoogle Scholar
  109. 109.
    Pestman JM, Terpstra KR, Stuart MCA, van Doren HA, Brisson A, Kellogg RM, Engberts JBFN (1997) Langmuir 13:6857CrossRefGoogle Scholar
  110. 110.
    Johnsson M, Wagenaar A, Engberts JB (2003) J Am Chem Soc 125:757PubMedCrossRefGoogle Scholar
  111. 111.
    Bajaj A, Kondaiah P, Bhattacharya S (2008) Biomacromolecules 9:991PubMedCrossRefGoogle Scholar
  112. 112.
    Ewert KK, Evans HM, Zidovska A, Bouxsein NF, Ahmad A, Safinya CR (2006) J Am Chem Soc 128:3998PubMedCrossRefGoogle Scholar
  113. 113.
    Solodin I, Brown CS, Bruno MS, Chow CY, Jang EH, Debs RJ, Heath TD (1995) Biochemistry 34:13537PubMedCrossRefGoogle Scholar
  114. 114.
    Cheng J, Zeidan R, Mishra S, Liu A, Pun SH, Kulkarni RP, Jensen GS, Bellocq NC, Davis ME (2006) J Med Chem 49:6522PubMedCrossRefGoogle Scholar
  115. 115.
    Kumar VV, Pichon C, Refregiers M, Guerin B, Midoux P, Chaudhuri A (2003) Gene Ther 10:1206PubMedCrossRefGoogle Scholar
  116. 116.
    Singh RS, Goncalves C, Sandrin P, Pichon C, Midoux P, Chaudhuri A (2004) Chem Biol 11:713PubMedCrossRefGoogle Scholar
  117. 117.
    Majeti BK, Karmali PP, Reddy BS, Chaudhuri A (2005) J Med Chem 48:3784PubMedCrossRefGoogle Scholar
  118. 118.
    Sudholter EJR, Engberts JBFN, Hoekstra D (1979) J Am Chem Soc 102:2467CrossRefGoogle Scholar
  119. 119.
    van der Woude I, Wagenaar A, Meekel AA, ter Beest MB, Ruiters MH, Engberts JB, Hoekstra D (1997) Proc Natl Acad Sci USA 94:1160PubMedCrossRefGoogle Scholar
  120. 120.
    Pijper D, Bulten E, Smisterova J, Wagenaar A, Hoekstra D, Engberts JBFN, Hulst R (2003) Eur J Org Chem 22:4406CrossRefGoogle Scholar
  121. 121.
    Hulst R, Muizebelt I, Oosting P, van der Pol C, Wagenaar A, Smisterová J, Bulten E, Driessen C, Hoekstra D, Engberts JBFN (2004) Eur J Org Chem 4:835CrossRefGoogle Scholar
  122. 122.
    Scarzello M, Smisterová J, Wagenaar A, Stuart MC, Hoekstra D, Engberts JB, Hulst R (2005) J Am Chem Soc 127:10420PubMedCrossRefGoogle Scholar
  123. 123.
    Ilies MA, Seitz WA, Caproiu MT, Wentz M, Garfield RE, Balaban AT (2003) Eur J Org Chem 14:2645CrossRefGoogle Scholar
  124. 124.
    Ilies MA, Seitz WA, Ghiviriga I, Johnson BH, Miller A, Thompson EB, Balaban AT (2004) J Med Chem 47:3744PubMedCrossRefGoogle Scholar
  125. 125.
    Zhu L, Lu Y, Miller DD, Mahato RI (2008) Bioconjug Chem 19:2499PubMedCrossRefGoogle Scholar
  126. 126.
    Meers P (1999) Adv Drug Deliv Rev 53:265CrossRefGoogle Scholar
  127. 127.
    Guo X, Szoka FC Jr (2003) Acc Chem Res 36:335PubMedCrossRefGoogle Scholar
  128. 128.
    Wolff JA, Rozema DB (2008) Mol Ther 16:8PubMedCrossRefGoogle Scholar
  129. 129.
    Oupický D, Diwadkar V (2003) Curr Opin Mol Ther 5:345PubMedGoogle Scholar
  130. 130.
    Tang FX, Hughes JA (1999) Bioconjugate Chem 10:791CrossRefGoogle Scholar
  131. 131.
    Balakirev M, Schoehn G, Chroboczek J (2000) Chem Biol 7:813PubMedCrossRefGoogle Scholar
  132. 132.
    Byk G, Wetzer B, Frederic M, Dubertret C, Pitard B, Jaslin G, Scherman D (2000) J Med Chem 43:4377PubMedCrossRefGoogle Scholar
  133. 133.
    Huang Z, Li W, MacKay JA, Szoka FC Jr (2005) Mol Ther 11:409PubMedCrossRefGoogle Scholar
  134. 134.
    Zhu J, Munn RJ, Nantz MH (2000) J Am Chem Soc 122:2645CrossRefGoogle Scholar
  135. 135.
    Huang Z, Guo X, Li W, MacKay JA, Szoka FC Jr (2006) J Am Chem Soc 128:60PubMedCrossRefGoogle Scholar
  136. 136.
    Chen H, Zhang H, McCallum CM, Szoka FC Jr, Guo X (2007) J Med Chem 50:4269PubMedCrossRefGoogle Scholar
  137. 137.
    Boomer JA, Thompson DH, Sullivan SM (1997) Pharm Res 19:1292CrossRefGoogle Scholar
  138. 138.
    Boomer JA, Qualls MM, Inerowicz HD, Haynes RH, Patri VS, Kim JM, Thompson DH (2009) Bioconjug Chem 20:47PubMedCrossRefGoogle Scholar
  139. 139.
    Liu D, Hu J, Qiao W, Li Z, Zhang S, Cheng L (2005) Bioorg Med Chem Lett 15:3147PubMedCrossRefGoogle Scholar
  140. 140.
    Savva M, Chen P, Aljaberi A, Selvi B, Spelios M (2005) Bioconjug Chem 16:1411PubMedCrossRefGoogle Scholar
  141. 141.
    Aissaoui A, Martin B, Kan E, Oudrhiri N, Hauchecorne M, Vigneron JP, Lehn JM, Lehn P (2004) J Med Chem 47:5210PubMedCrossRefGoogle Scholar
  142. 142.
    Knorr V, Allmendinger L, Walker GF, Paintner FF, Wagner E (2007) Bioconjug Chem 18:1218PubMedCrossRefGoogle Scholar
  143. 143.
    Wong JB, Grosse S, Tabor AB, Hart SL, Hailes HC (2008) Mol Biosyst 4:532PubMedCrossRefGoogle Scholar
  144. 144.
    Zhu M-Z, Wu Q-H, Zhang G, Ren T, Liu D, Guo Q-X (2002) Bull Chem Soc Jpn 75:2207CrossRefGoogle Scholar
  145. 145.
    Corey EJ, Raju N (1983) Tetrahedron Lett 24:5571CrossRefGoogle Scholar
  146. 146.
    Meth-Cohn O (1986) J Chem Soc Chem Commun 9:695Google Scholar
  147. 147.
    Murphy JE, Uno T, Hamer JD, Cohen FE, Dwarki V, Zuckermann RN (1998) Proc Natl Acad Sci USA 95:1517PubMedCrossRefGoogle Scholar
  148. 148.
    Huang CY, Uno T, Murphy JE, Lee S, Hamer JD, Escobedo JA, Cohen FE, Radhakrishnan R, Dwarki V, Zuckermann RN (1998) Chem Biol 5:345PubMedCrossRefGoogle Scholar
  149. 149.
    Choi JS, Lee EJ, Jang HS, Park JS (2000) J Biochem Mol Biol 33:476Google Scholar
  150. 150.
    Choi JS, Lee EJ, Jang HS, Park JS (2001) Bioconjug Chem 12:108PubMedCrossRefGoogle Scholar
  151. 151.
    Yingyongnarongkul BE, Howarth M, Elliott T, Bradley M (2004) J Comb Chem 6:753PubMedCrossRefGoogle Scholar
  152. 152.
    Liberska A, Unciti-Broceta A, Bradley M (2009) Org Biomol Chem 7:61PubMedCrossRefGoogle Scholar
  153. 153.
    Kish PE, Tsume Y, Kijek P, Lanigan TM, Hilfinger JM, Roessler BJ (2007) Mol Pharm 4:95PubMedCrossRefGoogle Scholar
  154. 154.
    Byk G, Frederic M, Scherman D (1997) Tetrahedron Lett 38:3219CrossRefGoogle Scholar
  155. 155.
    Byk G, Soto J, Mattler C, Frederic M, Scherman D (1998) Biotechnol Bioeng 61:81PubMedCrossRefGoogle Scholar
  156. 156.
    Oliver M, Jorgensen MR, Miller A (2004) Tetrahedron Lett 45:3105CrossRefGoogle Scholar
  157. 157.
    Lenssen K, Jantscheff P, Von Kiedrowski G, Massing U (2002) Chembiochem 3:852, Combinatorial synthesis of new cationic lipids and high-throughputPubMedCrossRefGoogle Scholar
  158. 158.
    Yingyongnarongkul BE, Howarth M, Elliott T, Bradley M (2004) Chemistry Eur J 10:463CrossRefGoogle Scholar
  159. 159.
    Yingyongnarongkul BE, Radchatawedchakoon W, Krajarng A, Watanapokasin R, Suksamrarn A (2009) Bioorg Med Chem 17:176PubMedCrossRefGoogle Scholar
  160. 160.
    Fara MA, Diaz-Mochon JJ, Bradley M (2006) Tetrahedron Lett 47:1011CrossRefGoogle Scholar
  161. 161.
    Unciti-Broceta A, Diezmann F, Ou-Yang CY, Fara MA, Bradley M (2009) Bioorg Med Chem 17:959PubMedCrossRefGoogle Scholar
  162. 162.
    Lebreton S, Newcombe N, Bradley M (2002) Tetrahedron Lett 43:2479CrossRefGoogle Scholar
  163. 163.
    Fréchet JMJ, Tomalia DA (eds) (2001) Dendrimers and other dendritic polymers. Wiley, ChichesterGoogle Scholar
  164. 164.
    Newkome GR, Moorefield CN, Vögtle F (eds) (2001) Dendrimers and dendrons. Concepts, synthesis and applications. Wiley-VCH, WeinheimGoogle Scholar
  165. 165.
    Grinstaff MW (2002) Chem Eur J 8:2839PubMedGoogle Scholar
  166. 166.
    Svenson S, Tomalia DA (2005) Adv Drug Deliv Rev 57:2106PubMedCrossRefGoogle Scholar
  167. 167.
    Fréchet JMJ, Mackay JA, Cameron CL, Szoka FC (2005) Nature Biotech 23:1517CrossRefGoogle Scholar
  168. 168.
    Eisler S, Diederich F, Guillot-Niecowski M (2007) New J Chem 31:1111CrossRefGoogle Scholar
  169. 169.
    Grayson SM, Fréchet JM (2001) Chem Rev 101:3819PubMedCrossRefGoogle Scholar
  170. 170.
    Smith DK (2003) Tetrahedron 59:3797CrossRefGoogle Scholar
  171. 171.
    Kehat T, Goren K, Portnoy M (2007) New J Chem 31:1218CrossRefGoogle Scholar
  172. 172.
    Antoni P, Nyström D, Hawker CJ, Hult A, Malkoch M (2007) Chem Commun 22:2249CrossRefGoogle Scholar
  173. 173.
    Boas U, Heegaard PMH (2004) Chem Soc Rev 33:43PubMedCrossRefGoogle Scholar
  174. 174.
    Medina SH, El-Sayed ME (2009) Chem Rev 109:3141PubMedCrossRefGoogle Scholar
  175. 175.
    Zhou J, Wu J, Hafdi N, Behr JP, Erbacher P, Peng L (2006) Chem Comm 22:2362PubMedCrossRefGoogle Scholar
  176. 176.
    Tang MX, Redemann CT, Szoka FC Jr (1996) Bioconj Chem 7:703CrossRefGoogle Scholar
  177. 177.
    Newkome GR, Shreiner CD (2008) Polymer 49:1CrossRefGoogle Scholar
  178. 178.
    Carlmark A, Hawker C, Hult A, Malkoch M (2009) Chem Soc Rev 38:352PubMedCrossRefGoogle Scholar
  179. 179.
    Buhleier E, Wehner W, Vögtle F (1978) Synthesis 155Google Scholar
  180. 180.
    Mülhaupt R, Wörner C (1993) Angew Chem Int Ed 32:1306CrossRefGoogle Scholar
  181. 181.
    Meijer EW, Brabander-van den Berg EMM (1993) Angew Chem Int Ed 32:1308CrossRefGoogle Scholar
  182. 182.
    Zinselmeyer BH, Mackay SP, Schatzlein AG, Uchegbu LF (2002) Pharm Res 19:960PubMedCrossRefGoogle Scholar
  183. 183.
    Hollins AJ, Benboubetra M, Omidi Y, Zinselmeyer BH, Schatzlein AG, Uchegbu IF, Akhtar S (2004) Pharm Res 21:458PubMedCrossRefGoogle Scholar
  184. 184.
    Schatzlein AG, Zinselmeyer BH, Elouzi A, Dufes C, Chim YTA, Roberts CJ, Davies MC, Munro A, Gray AI, Uchegbu IF (2005) J Control Release 101:247PubMedCrossRefGoogle Scholar
  185. 185.
    Tack F, Bakker A, Maes S, Dekeyser N, Bruining M, Elissen-Roman C, Janicot M, Brewster M, Janssen HM, De Waal BF, Fransen PM, Lou X, Meijer EW (2006) J Drug Target 14:69PubMedCrossRefGoogle Scholar
  186. 186.
    Baars MWPL, Kleppinger R, Koch MHJ, Yeu SL, Meijer EW (2000) Angew Chem Int Ed 39:1285CrossRefGoogle Scholar
  187. 187.
    Kim T-I, Baek JU, Bai CZ, Park JS (2007) Biomaterials 28:2061PubMedCrossRefGoogle Scholar
  188. 188.
    Tomalia DA, Baker H, Dewald J, Hall M, Kallos G, Martin S, Roeck J, Ryder J, Smith P (1985) Polym J 17:117CrossRefGoogle Scholar
  189. 189.
    Smith P, Ryder J, Roeck J, Martin J, Kallos G, Hall M, Dewald J, Baker H, Tomalia DA (1990) Angew Chem Int Ed 29:138CrossRefGoogle Scholar
  190. 190.
    Haensler J, Szoka FC Jr (1993) Bioconj Chem 4:372CrossRefGoogle Scholar
  191. 191.
    Kukowska-Latallo JF, Bielinska AU, Johnson J, Spindler R, Tomalia DA, Baker JR Jr (1996) Proc Natl Acad Sci USA 93:4897PubMedCrossRefGoogle Scholar
  192. 192.
    Sig Choi J, Nam K, Park J, Kin JB, Lee JK, Park J (2004) J Control Release 99:445, Grafting with lysine argineneCrossRefGoogle Scholar
  193. 193.
    Kono K, Akiyama H, Takahashi T, Takagishi T, Harada A (2005) Bioconj Chem 16:208CrossRefGoogle Scholar
  194. 194.
    Takahashi T, Kono K, Itoh T, Emi N, Takagishi T (2003) Bioconj Chem 14:764CrossRefGoogle Scholar
  195. 195.
    Takahashi T, Harada A, Emi N, Kono K (2005) Bioconj Chem 16:1160CrossRefGoogle Scholar
  196. 196.
    Arima H, Wada K, Kihara F, Tsutsumi T, Hirayama F, Uekama K (2002) J Inclusion Phenom Macrocyclic Chem 44:361CrossRefGoogle Scholar
  197. 197.
    Wada K, Arima H, Tsutsumi T, Chihara Y, Hattori K, Hirayama F, Uekama K (2005) J Control Release 104:397PubMedCrossRefGoogle Scholar
  198. 198.
    Wada K, Arima H, Tsutsumi T, Hirayama F, Uekama K (2005) Biol Pharm Bull 28:500PubMedCrossRefGoogle Scholar
  199. 199.
    Kihara F, Arima H, Tsutsumi T, Hirayama F, Uekama K (2002) Bioconj Chem 13:1211CrossRefGoogle Scholar
  200. 200.
    Wood KC, Azarin SM, Arap W, Pasqualini R, Langer R, Hammond PT (2008) Bioconj Chem 19:403CrossRefGoogle Scholar
  201. 201.
    Arima H, Kihara F, Hirayama F, Uekama K (2003) Bioconj Chem 12:476CrossRefGoogle Scholar
  202. 202.
    Sonawane ND, Szoka FC Jr, Verkman AS (2003) J Biol Chem 278:44826PubMedCrossRefGoogle Scholar
  203. 203.
    Leong KW, Mao HQ, Liu ZL, Zhuo RX, Huang SW, Wang XL, Zhang XQ (2005) Biomacromolecules 6:341PubMedCrossRefGoogle Scholar
  204. 204.
    Wu J, Zhou J, Qu F, Bao P, Zhang Y, Peng L (2005) Chem Commun 3:313CrossRefGoogle Scholar
  205. 205.
    Lee JW, Kim JH, Kim HJ, Han SC, Kim JH, Shin WS, Jin SH (2006) Macromolecules 39:2418, 9CrossRefGoogle Scholar
  206. 206.
    Lee JW, Kim JH, Kim HJ, Han SC, Kim JH, Shin WS, Jin SH (2007) Bioconj Chem 18:57Google Scholar
  207. 207.
    Kim TI, Seo HJ, Choi JS, Jang HS, Baek JU, Kim K, Park JS (2004) Biomacromolecules 5:2487PubMedCrossRefGoogle Scholar
  208. 208.
    Pittelkow M, Christensen JB (2005) Org Lett 7:1295PubMedCrossRefGoogle Scholar
  209. 209.
    Lukasavage WJ, Kolc J, Dankewalter RG (1981) US Patent 4(289):872Google Scholar
  210. 210.
    Ohsaki M, Okuda T, Wada A, Hirayami T, Niidome T, Aoyagi H (2002) Bioconj Chem 13:510CrossRefGoogle Scholar
  211. 211.
    Okuda T, Sugiyama A, Niidome T, Aoyagi H (2003) Biomaterials 25:537CrossRefGoogle Scholar
  212. 212.
    Kaneshiro TL, Wang X, Lu ZR (2007) Mol Pharmaceutics 4:759CrossRefGoogle Scholar
  213. 213.
    Loup C, Zanta MA, Caminade AM, Majoral JP, Meunier B (1999) Chem Eur J 5:3644CrossRefGoogle Scholar
  214. 214.
    Galliot C, Prevote D, Caminade AM, Majoral JP (1995) J Am Chem Soc 117:5470CrossRefGoogle Scholar
  215. 215.
    Bermejo JF, Ortega P, Chonco L, Eritja R, Samaniego R, Muellner M, de Jesus E, de la Mata JF, Flores JC, Gomez R, Munoz-Fernandez A (2007) Chem Eur J 13:483PubMedCrossRefGoogle Scholar
  216. 216.
    Mintzer MA, Merkel OM, Kissel T, Simanek EE (2009) New J Chem 33:1918PubMedCrossRefGoogle Scholar
  217. 217.
    Ma X, Tang J, Shen Y, Fan M, Tang H, Radosz M (2009) J Am Chem Soc 131:14795PubMedCrossRefGoogle Scholar
  218. 218.
    Joester D, Losson M, Pugin R, Heinzelmann H, Walter E, Merkle HP, Diederich F (2003) Angew Chem Int Ed Engl 42:1486PubMedCrossRefGoogle Scholar
  219. 219.
    Wells NJ, Basso A, Bradley M (1998) Biopolymers (Peptide Science) 47:381CrossRefGoogle Scholar
  220. 220.
    Swali V, Wells NJ, Langley GJ, Bradley M (1997) J Org Chem 62:4902CrossRefGoogle Scholar
  221. 221.
    Monaghan S, Griffith-Johnson D, Matthews I, Bradley M (2001) ARKIVOC Part 10, pp 46–53Google Scholar
  222. 222.
    Tam JP (1988) Proc. Natl Acad Sci USA 85:5409CrossRefGoogle Scholar
  223. 223.
    Wimmer N, Marano RJ, RJ KPS, Rakoczy EP, Toth I (2002) Bioorg Med Chem Lett 12:2635PubMedCrossRefGoogle Scholar
  224. 224.
    Choi JS, Joo DK, Kim CH, Kim K, Park JS (2000) J Am Chem Soc 122:474CrossRefGoogle Scholar
  225. 225.
    Parekh HS, Marano RJ, Rakoczy EP, Blanchfield J, Toth I (2006) Bioorg Med Chem 14:4775PubMedCrossRefGoogle Scholar
  226. 226.
    Peretto I, Sanchez-Martin RM, Wang X, Ellard J, Mittoo S, Bradley M (2003) Chem Commun 18:2312CrossRefGoogle Scholar
  227. 227.
    Diaz-Mochon JJ, Fara MA, Sanchez-Martin RM, Bradley M (2007) Tet Lett 49:923CrossRefGoogle Scholar
  228. 228.
    Chighine A, Sechi G, Bradley M (2007) Drug Discov Today 12:459PubMedCrossRefGoogle Scholar
  229. 229.
    Kappe CO, Dallinger D (2009) Mol Diversity 13:71CrossRefGoogle Scholar
  230. 230.
    Lebreton S, Monaghan S, Bradley M (2001) Aldrichimica Acta 34:75Google Scholar
  231. 231.
    Lebreton S, How SE, Buchholz M, Yingyongnarongkul BE, Bradley M (2003) Tetrahedron 59:3945CrossRefGoogle Scholar
  232. 232.
    How SE, Yingyongnarongkul B, Fara MA, Diaz-Mochon JJ, Mittoo S, Bradley M (2004) Comb Chem HT Screen 7:423Google Scholar
  233. 233.
    Ternon M, Diaz-Mochon JJ, Belsom A, Bradley M (2004) Tetrahedron 60:8721CrossRefGoogle Scholar
  234. 234.
    How SE, Unciti-Broceta A, Sánchez-Martín RM, Bradley M (2008) Org Biomol Chem 6:2266PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Asier Unciti-Broceta
    • 1
    Email author
  • Matthew N. Bacon
    • 1
  • Mark Bradley
    • 1
  1. 1.School of ChemistryUniversity of EdinburghEdinburghUK

Personalised recommendations