Synthesis and interfacial properties of amphiphilic
b-cyclodextrins and their substitution at the O-6 position with a
mono bio-recognisable galactosyl antenna
Alain Salameh,
a
Adina N. Lazar,
b
Anthony W. Coleman
b
and He
´
le
`
ne Parrot-Lopez
a,
*
a
Me
´
thodologie de Synthe
`
se et Mole
´
cules Bioactives, UMR-CNRS 5181, Universite
´
Claude Bernard-Lyon 1,
Domaine Scientifique de la Doua, Ba
ˆ
t. J. Raulin, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne cedex, France
b
Institut de Biologie et Chimie des Prote
´
ines, CNRS-UMR 5086, 7 passage du Vercors, Lyon cedex 07, 69367, France
Received 8 April 2005; revised 9 June 2005; accepted 16 June 2005
Abstract—The synthesis of a mono-galactosylated amphiphilic b-cyclodextrin, in five steps from mono-6-azido-6-deoxy-b-cyclodextrin,
via coupling to a N-b-
D
-galactopyranosylamino-antenna is described. Both characterization by electrospray mass spectrometry and NMR
show the presence of only the mono-substituted product. The Langmuir isotherms of the final product and intermediates are described.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
b-Cyclodextrins (b-CDs) or cyclomaltoheptaoses have long
been recognized to have significant potential as drug carriers
arising from their ability to form inclusion complexes.
1
Inclusion of the bioactive molecules generates several
therapeutic advantages: solubilisation of poorly soluble or
insoluble molecules,
2
protection from chemical and
enzymatic degradation,
3
transport and time control of
release.
4
Currently, in order to reduce the appearance of
resistance towards therapeutic agents and to decrease the
toxicity of the bioactive molecules, several studies have
been undertaken to target such carriers, reducing in this way
the quantity of drug used in therapies. Carbohydrates are
biocompatible molecules having low immunogenicity and
are responsible of recognition between the cells. We have
previously demonstrated the capacity of galactosyl-b-
cyclodextrin to be recognized by a galactosyl specific cell
wall lectin Kluyveromyces bulgaricus (KbCWL)
5
and in the
literature there exist several reports of the synthesis of
cyclodextrin derivatives substituted with mono or poly-
saccharides and which have shown to be recognized by
lectins.
6
Recently, chemo-enzymatic synthesis of amphi-
philic cyclodextrins fully substituted with N-acetyl-gluco-
samine (Glc-NAc) has been described.
7
Indeed to pass from a system of 1:1 complexation to
nanoparticles able to ensure a much higher degree of
encapsulation, the use of amphiphilic cyclodextrins has
been developed. In the previous studies, amphiphilic
cyclodextrins were obtained by the introduction of
lipophilic groups at the primary face and/or secondary
face.
8
These amphiphilic cyclodextrins are capable of
forming liposomes,
9
nanoparticles,
10
vesicles,
11
micellar
aggregates
12
and solid lipid nanoparticles.
13
The objective of the current work resides in the combination
of the recognition properties of the mono-galactosyl-b-
cyclodextrins and their amphiphilic properties to obtain new
carrier molecules containing a galactosyl antenna at the O-6
position and lipophilic ester groups at the O-2 and O-3
positions. The synthesis, characterization and the interfacial
properties of these molecules as Langmuir monolayers are
described.
2. Results and discussion
2.1. Synthesis and characterization
In previous studies we have demonstrated good recognition
capacity (1.75 mmol dm
K3
) towards a galactose specific
yeast lectin K. bulgaricus (Kb CWL) of a mono-galactosyl-
b-CD derived from mono-6-amino-6-deoxy-b-CD by
coupling a galactosyl head group via a spacer chain (9
carbon atoms). In contrast to expectations, a ‘clustering
Tetrahedron 61 (2005) 8740–8745
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.054
Keywords: Amphiphilic cyclodextrin; Galactosyl antenna; Langmuir
isotherms.
*
Corresponding author. Tel.: C33 472431532; fax: C33 472448438;
e-mail: h.parrot@cdlyon.univ-lyon1.fr