Download PDF
Synthesis 2011(18): 2968-2974  
DOI: 10.1055/s-0030-1260151
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Design and Synthesis of a Multivalent Heterobifunctional CD22 Ligand as a Potential Immunomodulator

Hajjaj H. M. Abdu-Allah*a,b, Kozo Watanabec, Shusaku Daikokud, Osamu Kanied, Takeshi Tsubatac, Hiromune Andoa,e, Hideharu Ishidaa, Makoto Kiso*a,e
a Department of Applied Bio-organic Chemistry, The United Graduate School of Agricultural Sciences, Gifu University, Gifu 501-1193, Japan
Fax: +81(58)2932840; e-Mail: kiso@gifu-u.ac.jp; e-Mail: moazhajjaj@yahoo.com;
b Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
c Laboratory of Immunology, School of Biomedical Science, Tokyo Medical and Dental University, Japan
d Japan Science and Technology Agency (JST), ERATO, Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan
e Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8501, Japan
Further Information

Publication History

Received 21 April 2011
Publication Date:
05 August 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

We describe the design and synthesis of a trivalent CD22 ligand conjugated with a trivalent nitrophenol (ligand for decameric anti-nitrophenol immunoglobulin M). To generate such a bifunctional ligand, we designed and prepared two synthetic building blocks possessing different terminal functionalities. Coupling of these compounds afforded a trivalent azide-terminated scaffold. Ligation of the scaffold with an alkyne-terminated CD22 ligand by the use of click chemistry afforded the target trivalent cluster. We anticipate that our ligand will be valuable in a variety of applications, including targeting B cells and modulation of the humoral immune response.

Key words

bifunctional ligand - multivalent compounds - CD22 - targeting - coupling - click chemistry

    References

  • 1 Boas U. Heeg PM. Chem. Soc. Rev.  2004,  33:  43 
    CrossrefPubMedGoogle Scholar
  • 2 Puffer EB. Pontrello JK. Hollenbeck JJ. Kink JA. Kiessling LL. ACS Chem. Biol.  2007,  2:  252 
    CrossrefPubMedGoogle Scholar
  • 3 Kitov PI. Lipinski T. Paszkiewicz E. Solomon D. Sadowska JM. Grant GA. Mulvey GL. Kitova EN. Klassen JS. Armstrong GD. Bundle DR. Angew. Chem. Int. Ed.  2008,  47:  672 
    CrossrefPubMedGoogle Scholar
  • 4 Kiessling LL. Gestwicki JE. Strong LE. Angew. Chem. Int. Ed.  2006,  45:  2348 
    CrossrefPubMedGoogle Scholar
  • 5 Corson TW. Aberle N. Crews CM. ACS Chem. Biol.  2008,  3:  677 
    CrossrefPubMedGoogle Scholar
  • 6 Solomon D. Kitov PI. Paszkiewicz E. Grant GA. Sadowska JM. Bundle DR. Org. Lett.  2005,  7:  4369 
    CrossrefPubMedGoogle Scholar
  • 7 Liu J. Zhang Z. Tan X. Hol WGJ. Verlinde CLMJ. Fan E. J. Am. Chem. Soc.  2005,  127:  2044 
    CrossrefPubMedGoogle Scholar
  • 8 Courtney AH. Puffer EB. Pontrello JK. Yang Z. Kiessling LL. Proc. Natl. Acad. Sci. U.S.A.  2009,  106:  5247 
    Google Scholar
  • 9 Owen RM. Carlson CB. Xu J. Mowery P. Fasella E. Kiessling LL. ChemBioChem  2007,  8:  68 
    CrossrefPubMedGoogle Scholar
  • 10 Duong BH. Tian H. Ota T. Completo G. Han S. Vela JL. Ota M. Kubitz M. Bovin N. Paulson JC. Nemazee D. J. Exp. Med.  2010,  207:  173 
    CrossrefPubMedGoogle Scholar
  • 11 Gestwicki JE. Crabtree GR. Graef IA. Science (Washington, D.C.)  2004,  306:  865 
    CrossrefPubMedGoogle Scholar
  • 12 Lu Y. Low PS. Cancer Immunol. Immunother.  2002,  51:  153 
    CrossrefPubMedGoogle Scholar
  • 13a Steinfeld SD. Tant L. Burmester GR. Teoh NK. Wegener WA. Goldenberg DM. Pradier O. Arthritis Res. Ther.  2006,  8:  R129 
    Google Scholar
  • 13b Fiorina P. Vergani A. Dada S. Jurewicz M. Wong M. Law K. Wu E. Tian Z. Abdi R. Guleria I. Rodig S. Dunussi-Joannopoulos K. Bluestone J. Sayegh MH. Diabetes  2008,  57:  3013 
    Google Scholar
  • 14 Razi N. Varki A. Proc. Natl. Acad. Sci. U.S.A.  1998,  95:  7469 
    CrossrefPubMedGoogle Scholar
  • 15 Powell LD. Jain RK. Matta KL. Sabesan S. Varki A. J. Biol. Chem.  1995,  270:  7523 
    CrossrefPubMedGoogle Scholar
  • 16 Collins BE. Blixt O. Han S. Duong B. Li H. Nathan JK. Bovin N. Paulson JC. J. Immunol.  2006,  177:  2994 
    CrossrefPubMedGoogle Scholar
  • 17a O’Reilly MK. Collins BE. Han S. Liao L. Rillahan C. Kitov PI. Bundle DR. Paulson JC. J. Am. Chem. Soc.  2008,  130:  7736 
    Google Scholar
  • 17b Cui L. Kitov PI. Completo GC. Paulson JC. Bundle DR. Bioconjugate Chem.  2011,  22:  546 
    Google Scholar
  • 18 Browning JL. Nat. Rev. Drug Discovery  2006,  5:  564 
    CrossrefPubMedGoogle Scholar
  • 19 Abdu-Allah HHM. Tamanaka T. Yu J. Zhuoyuan L. Sadagopan M. Adachi T. Tsubata T. Kelm S. Ishida H. Kiso M. J. Med. Chem.  2008,  51:  6665 
    CrossrefPubMedGoogle Scholar
  • 20 Abdu-Allah HHM. Watanabe K. Hayashizaki K. Iwayama Y. Takematsu H. Kozutsumi Y. Tsubata T. Ishida H. Kiso M. Tetrahedron Lett.  2009,  50:  4488 
    CrossrefGoogle Scholar
  • 21 Newkome GR. Moorefield CN. Baker GR. Aldrichimica Acta  1992,  25:  31 
    Google Scholar
  • 22 Ashton PR. Boyd SE. Brown CL. Jayaraman N. Nepogodiev SA. Stoddart JF. Chem. Eur. J.  1996,  2:  1115 
    CrossrefGoogle Scholar
  • 23 Diaz DD. Punna S. Holzer P. McPherson AK. Sharpless KB. Fokin VV. Finn MG. J. Polym. Sci., Part A: Polym. Chem.  2004,  42:  4392 
    CrossrefGoogle Scholar
  • 24 Atkinson SJ. Ellis V.-J. Boyd SE. Brown C. New J. Chem.  2007,  31:  155 
    CrossrefGoogle Scholar
  • 25 Martinu T. Dailey WP. J. Org. Chem.  2000,  65:  6784 
    CrossrefPubMedGoogle Scholar
  • 26 G irault I. Karu AE. Schaper M. Barcellos-Hoff MH. Hagen T. Vogel DS. Ames BN. Christen S. Shigenaga MK. Free Radical Biol. Med.  2001,  31:  1375 
    CrossrefPubMedGoogle Scholar
  • 27 Fernandez-Megia E. Correa J. Rodríguez-Meizoso I. Riguera R. Macromolecules  2006,  39:  2113 
    CrossrefGoogle Scholar
  • 28 Meunier SJ. Wu Q. Wang S.-N. Roy R. Can. J. Chem.  1997,  75:  1472 
    CrossrefGoogle Scholar
  • 29a Malkoch M. Schleicher K. Drockenmuller E. Hawker CJ. Russell TP. Wu P. Fokin VV. Macromolecules  2005,  38:  3663 
    Google Scholar
  • 29b Joosten JAF. Tholen NTH. Maate FAL. Brouwer AJ. van Esse GW. Rijkers DTS. Liskamp RMJ. Pieters RJ. Eur. J. Org. Chem.  2005,  3182 
    Google Scholar
  • 30a Rostovtsev VV. Green LG. Fokin VV. Sharpless KB. Angew. Chem. Int. Ed.  2002,  41:  2596 
    Google Scholar
  • 30b Speers AE. Adam GC. Cravatt BF. J. Am. Chem. Soc.  2003,  125:  4686 
    Google Scholar
  • 30c Link AJ. Tirrell DA. J. Am. Chem. Soc.  2003,  125:  11164 
    Google Scholar
  • 30d Helms B. Mynar JL. Hawker CJ. Fréchet JMJ. J. Am. Chem. Soc.  2004,  126:  15020 
    Google Scholar
  • 30e Punna S. Kuzelka J. Wang Q. Finn MG. Angew. Chem. Int. Ed.  2005,  44:  2215 
    Google Scholar
  • 30f Parrish B. Breitenkamp RB. Emrick T. J. Am. Chem. Soc.  2005,  127:  7404 
    Google Scholar
  • 30g Rodionov VO. Fokin VV. Finn MG. Angew. Chem. Int. Ed.  2005,  44:  2210 
    Google Scholar
  • 31 Kolb HC. Finn MG. Sharpless KB. Angew. Chem. Int. Ed.  2001,  40:  2004 
    CrossrefPubMedGoogle Scholar
  • 32a Crich D. Smith M. J. Am. Chem. Soc.  2001,  123:  9015 
    Google Scholar
  • 32b Crich D. Karatholuvhu SM. J. Org. Chem.  2008,  73:  5173 
    Google Scholar
  • 33 Daikoku S. Kurimoto A. Mutsuga S. Ako T. Kanemitsu T. Shioiri Y. Ohtake A. Kato R. Saotome C. Ohtsuka I. Koroghi S. Sarkar SK. Tobe A. Adachi S. Suzuki K. Kanie O. Carbohydr. Res.  2009,  344:  384 
    CrossrefPubMedGoogle Scholar