CLICK CHEMISTRY APPLIED TO CARBOHYDRATE-BASED DRUG DISCOVERY - Click Chemistry in Glycoscience: New Developments and Strategies - page 316

13

CLICK CHEMISTRY APPLIED
TO CARBOHYDRATE-BASED
DRUG DISCOVERY

VANESSA LEIRIA CAMPO AND IVONE CARVALHO

13.1 INTRODUCTION

The discovery of new bioactive molecules based on screening of analog libraries and
structure-activity relationship has been accomplished by a range of chemical proce-
dures, in which the cycloadditions, particularly the Huisgen 1,3-dipolar cycloaddi-
tion catalyzed by Cu(I), designated as “copper-catalyzed azide/alkyne cycloaddition”
(CuAAC), are the most extensively utilized “click chemistry” [1-3]. These reactions
are easily performed, fast, highly selective, insensitive to oxygen and water, do not
require excessive chromatographic purifications, and can lead to great structural diver-
sity in high yields. Moreover, the physicochemical properties of the formed triazole
group are particularly favorable, since it acts as a rigid link, displaying pharmacophore
groups in well-defined spatial orientation, and neither hydrolyzable, oxidizable, or
reducible [3, 4]. Concerning carbohydrate chemistry, CuAAC reactions have been
increasingly applied for synthesis of carbohydrates and neoglycoconjugates directed
to the understanding of biological pathways mechanisms and drug discovery, includ-
ing the generation of potential substrates/inhibitors for a range of different enzymes,
glycopolymers able to establish multivalent interactions with defined target proteins
and biological probes for selective labeling of biomolecules either in cells or within
living organisms [5, 6].