TOWARD IMAGING GLYCOTOOLS BY CLICK COUPLING - Click Chemistry in Glycoscience: New Developments and Strategies - page 186

25

AcO
AcO
AcO

AcO
Ac AcO

N

O

O FmocNH COO H N

N

N 3

Na-ascorbate OAc

OAc

SPPS

Cu(OAc) 2

24 t BuOH/H O

2

26 FmocNH COOH

NH

NH
NH 2

HO
HO
HO

HO
H HO

O N

HN N HN NH 2

O

N

O N

O O

OH

OH

O

O

NH HN

NH HN

29 X = H 27 X = H

O O

30 X = 125 I 28 X = 125 I

NH HN

NH HN

N

N

O

O

O O

X

HO X HO

COOH

COOH

SCHEME 7.5 Synthesis of glycosylated cRGD peptide using CuAAC.

were tested as ligands of human v 3 integrin in a solid-phase assay by competition

binding with radioactive of 111 In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic
acid (DOTA)-E-[ c (RGDfK)] as the reference compound. IC 50 of 144nM for 27 and
238 nM for 29 were measured, in the same range of the Kessler's peptide c (RGDfV)
[56] at 65 nM, indicating that side chain modification had only limited effect on
the affinity. Imaging tools were built from 27 and 29 by standard iodination of the
tyrosine residue with 125 I. It has been shown that the radiolabeled compounds 28 and
30 accumulate in tumors and that this accumulation is mediated by

v 3 integrin.
Furthermore, compound 27 with the triazole ring showed improved pharmacological
properties with reduced liver and higher tumor uptakes. This study confirms the
nondeleterious effect of glycosylation via triazole ring formation.

7.3.2.2 Radiotracers Based on Metal Chelates Metal complexes are key com-
pounds in molecular imaging because of the use of radiometals in SPECT ( 99m Tc,
111 In, 186 Re, etc.) or in PET ( 64 Cu), these elements being included in complexing
moieties often made of nitrogen heterocycles or macrocycles. In this regard, the
triazole ring is interesting because it could be involved in part in cooperation with
other groups in such metal complexes. In 2006, the group of Schibli introduced the
“click to chelate” approach in which the synthesis of the complexing moiety and its
complexation is achieved in a single step making use of the CuAAC method (Scheme
7.6) [57]. This approach has been tested on two azido sugars, 3 -azido thymidine
31 and 1-azido-1-deoxy-

-D-galactopyranose 32 reacting with propargyl-glycine in
aqueous solutions at 100 ◦ C for 30 minutes in the presence of Cu(OAc) 2 and sodium