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OH
O
N
O
Asp-His-D-Phe-Arg-Trp-Gly-Lys-CONH
2
OH
HO
OR
N
O
H
H
3
C
HOOC
N
N
88
R = H
111
In
OH
N
N
O
HOOC
COOH
H
HO
89
R =
OH
HO
O
HO
HO
Glycosylation of
111
In labeled heptapetide using the Maillard reaction as a
SCHEME 7.18
click coupling.
-melanocyte-
stimulating hormone (MSH) analogs in order to improve the biokinetics of the
radiotracer based on
111
In complexation by DOTA (Scheme 7.18) [83]. Interest-
ingly, the
N
-terminus of a heptapeptide derived from
The Maillard reaction has been used for the glycosylation of
-MSH was glycosylated on
resin at the end of the peptide synthesis using ten equivalent of glucose in a mixture of
MeOH/AcOH (95:5) at 60
◦
C for 72 hours. Cleavage from the resin and coupling with
DOTA yielded after deprotection and complexation with
111
In, the radioligand
88
.
The glycosylation with maltotriose giving
89
was also reported. Other glycopeptides
have been prepared by glycosylation of the Lys residue of the same peptide under
Maillard conditions. The glycosylated peptides
88
and
89
showed increased kidney
reuptake and retention.
NT is a tridecapeptide localized in both the central nervous system and in the
gastrointestinal tract acting as a neurotransmitter and a hormone. One subtype of the
receptor of NT, the NTR1 receptors, is highly overexpressed on pancreatic carci-
noma cells. NT-based radiotracers are thus interesting tools to develop. In the search
for neurotensin-based radiotracers, Maes and Tourwe prepared glycosylated peptides
equipped with a
99m
Tc(CO)
3
chelator using Amadori rearrangement. On model pep-
tides, glycosylation occurred mainly at the
amino group of the lysine residue but
the secondary amine present in the histidine residue of the chelator could also be
glycosylated [84].
Bombesin is a tetradecapeptide isolated from a frog skin which binds to gastrin-
releasing peptide receptor, a receptor overexpressed in human prostate, breast, colon,
and small-cell lung carcinoma. Bombesin-based radiotracers have been prepared by
coupling this peptide with glucose and further complexation of the adduct with
99m
Tc
[85-87].
ε
7.4.2 Oxime Formation
Oxime formation is a useful rapid and traceless reaction which has found
numerous developments in chemical ligation of peptides and sugars [88] and in
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