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carbohydrate-protein interactions The self-assembled monolayer (SAM) scaffold
has appeared as one of the most promising model systems in this sense, because the
glyco-SAMs offer extensive control over density and orientation of the sugar ligands
and, more importantly, are amenable to real-time, label-free analysis methods such as
SPR, quartz crystal microbalance (QCM), ellipsometry or atomic force microscopy
(AFM). Glyco-SAMs can be prepared by direct sugar coating of preformed SAMs,
from which SAMs of alkanethiolates on gold currently hold the best model system.
CuAAC has once more proven its versatility by allowing a very efficient interphase
coupling reaction (“click on SAM”).
The groups of Wang and coworkers [164] and Lindhorst and coworkers [165]
privileged the use of propargylamido-terminated thiolates, generated from either
disulfides or thioacetate precursors, for the preparation of alkyne functional SAMs,
whereas Miura and coworkers [166] favored propargyl-ether-terminated disulfides.
These clickable SAMs were readily coupled with azido sugars, including mono-,
di-, or trisaccharides or even azide-armed, preformed glycodendrons, using stan-
dard Cu(I)-catalyzed conditions. Co-assembling the alkyne-functionalized thiolate
with a thiolate bearing irrelevant terminal groups was used to finely tune the sur-
face carbohydrate density. The glyco-SAMs thus obtained proved to be potent plat-
forms for high-throughput characterization of carbohydrate-lectin interactions. In
a more sophisticated application, Miura and coworkers used a click 6-
O
-sulfo-
N
-
acetylglucosamine (the most abundant structure of heparin) glycodendron-coated
SAM (
112
), obtained from the azide-armed trivalent click conjugate
110
and
the alkyne functional SAM
111,
by click on SAM (Scheme 6.21), to study the
mechanism of amyloidosis of Alzheimer amyloid
(1-42))
by AFM and SPR [167]. The results indicated that the multivalency of sugars
was significant regarding both the morphology and the aggregation effects of A
peptide (1-42) (A
(1-42). Other types of surfaces that have been made clickable by alkynylation in
order to be functionalized with carbohydrates include silicon, quartz, and glass
substrates [168], cellulose [169], polymeric surfaces (polystyrene, polyacrylamide,
poly(ethylene glycol), poly(2-ethyl-2-oxazoline, polypropylene) [170], and hydrogel
layers [171].
Several examples of preformation of click glycodendrons [172,173], glycoclusters
[174], or glycooligomers [175] endowed with a suitable functional moiety for their
attachment to a complementary surface have been reported and applied to the prepara-
tion of carbohydrate (micro)arrays displaying different sets of multivalent glycotopes.
Alternatively, “clicking-on” approaches have also demonstrated their efficiency for
such goals [176]. Wong and coworkers [177], in the very first report on the CuAAC
reaction in the field of glycosciences, already presented a proof of this concept. Thus,
N
-tetradecyl propargylamide was noncovalently bound to the surface of microtiter
plate wells and a series of azide-armed oligosaccharides was clicked at the interphase.
Interestingly, the clicked oligosaccharides could be further transformed in the well
by enzyme-assisted reactions. The “clicking-on” concept has been later extended
by Bertozzi and coworkers to the microcontact printing of alkyne-functionalized
glycopolymers on azide-functionalized silicon wafer chips [178].
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