ORGANIC
LETTERS
2005
Vol. 7, No. 17
3753-3756
Pentaerythritol as the Core of
Multivalent Glycolipids: Synthesis of a
Glycolipid with Three SO3Lea Ligands
Jie Xue,†,‡ Junmin Zhu,§ Roger E. Marchant,*,§ and Zhongwu Guo*,†,‡
Departments of Chemistry and Biomedical Engineering, Case Western ReserVe
UniVersity, 10900 Euclid AVenue, CleVeland, Ohio 44106-7078, and Department of
Chemistry, Wayne State UniVersity, 5101 Cass AVenue, Detroit, Michigan 48202
Received June 18, 2005
ABSTRACT
A glycolipid containing three SO3Lea ligands was synthesized with pentaerythritol as the core. The glycolipid was used to prepare glycoliposomes
that showed stability similar to that of DSPC liposomes without glycolipid. The easily prepared derivatives of pentaerythritol proved to be
useful scaffolds for multivalent displaying of carbohydrates in the form of glycolipids and clustered glycoliposomes.
While carbohydrate-protein interactions shape the basis of
glycobiology,1 the significant enhancement of these interac-
tions by the so-called “multivalent effect” is critical to various
biological functions.2,3 It is believed that nature uses this
mechanism to offset the generally low affinity of carbohy-
drate ligands for their protein receptors. Actually, compelling
results have revealed that clustering multiple carbohydrate
binding motifs in a glycoconjugate ligand can dramatically
increase its protein affinity.3,4
Recently, a wide range of multivalent glycoconjugates
have been designed, prepared, and studied,3,4 of which the
majority are dendrimers with multiple carbohydrate ligands
anchored to peptides, acrylamides, or other multifunctional
cores. Another important form of multivalent presentation
of carbohydrate ligands is glycoliposomes, i.e., liposomes
decorated with carbohydrates,5-7 such as the display of
selectin ligands on liposome surfaces.8-11 A unique property
of this latter approach is that liposomes can offer superb
structural versatility in terms of chemical composition and
molecular fluidity, allowing self-assembly of glycolipids to
form special carbohydrate domains on liposome surfaces.
Thus, glycoliposomes have been studied extensively as tools
for targeted delivery of drugs,5-7 which makes use of the
specific interactions between carbohydrate ligands on a
glycoliposome and the particular receptors on the targeted
tissue.
In an effort to develop a useful system for the targeted
delivery of drugs to inflammatory tissues, we have recently
studied the stability and other properties of glycoliposomes
made of a monovalent glycolipid of SO3Lea,12 the natural
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(8) Spevack, W.; Foxall, C.; Charych, D. H.; Dasgupa, F.; Nagy, J. O.
J. Med. Chem. 1996, 39, 1018-1020.
† Department of Chemistry, Case Western Reserve University.
‡ Wayne State University.
(9) DeFrees, S. A.; Philips, L.; Guo, L.; Zalipsky, S. J. Am. Chem. Soc.
1996, 118, 6101-6102.
§ Department of Biomedical Engineering, Case Western Reserve Uni-
versity.
(10) Sun, X.; Kanie, Y.; Guo, C.; Kanie, O.; Suzuki, Y.; Wong, C.-H.
Eur. J. Org. Chem. 2000, 14, 2643-2653.
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(2) Lee, R. T.; Lee, Y. C. Glycoconjugate J. 2000, 17, 543-551.
(3) Lundquist, J. J.; Toone, E. J. Chem. ReV. 2002, 102, 555-578.
(4) Roy, R. Trends Glycosci. Glycotechnol. 2003, 15, 291-310.
(5) Kawakami, S.; Yamashita, F.; Nishida, K.; Nakamura, J.; Hashida,
M. Crit. ReV. Ther. Drug Carrier Syst. 2002, 19, 171-190.
(11) Bruehl, R. E.; Dasgupta, F.; Katsumoto, T. R.; Tan, J. H.; Bertozzi,
C. R.; Spevak, W.; Ahn, D. J.; Rosen, S. D.; Nagy, J. O. Biochemistry
2001, 40, 5964-5974.
(12) Yan, F.; Xue, J.; Zhu, J.; Marchant, R. E.; Guo, Z. Bioconjugate
Chem. 2005, 16, 90-96.
10.1021/ol0514202 CCC: $30.25
© 2005 American Chemical Society
Published on Web 07/19/2005