Biomedical Engineering Reference
In-Depth Information
Our first contribution to this field was a novel family of
geometrically differing lipopolyamines [20-22]. We have exploited,
for the first time, solid-phase combinatorial chemistry to obtain a
variety of geometrically varied mono-functionalized polyamines
as building blocks for generating the structurally different
lipopolyamines. The use of a solid phase support for the synthesis of
geometrically varied polyamines significantly simplifies the number
of steps in the synthesis [23-25]. Thus, taking advantage of a
dilution effect obtained by linking a bromo-acetyl group to a
solid phase support, a variety of mono-functionalized protected
polyamines were rapidly obtained in a single step without isolating
any intermediate. After cleavage from the solid support, the free
carboxylic function of the building blocks was reacted with the
appropriate linkers and lipids to obtain the desired products
(see Fig. 1.3).
O
O
O
H
O
H
N
N
B
o
c
N
B
o
c
N
B
o
c
B
o
c
H
N
N
B
o
c
B
o
c
H
N
N
B
o
c
H
N
N
H
H
N
N
2
2
H
O
O
Br
H
N
N
H
H
N
N
H
2
2
Cl
2
2
N
N
N
H
H
N
N
2
2
N
H
2
O
B
o
c
H
N
N
H
B
o
c
O
H
B
o
c
H
N
N
B
o
c
H
N
N
N
O
H
B
o
c
H
N
N
O
N
H
B
o
c
Figure 1.
Synthesis of geometrically varied mono-functionalized
polyamine building blocks for the synthesis of geometrically
varied lipopolyamines.
The polyamine, the spacer, and the lipid moiety of the
lipopolyamines were systematically modified, and the impact of
these modifications on gene delivery was demonstrated
in vitro
on several cell lines and
for selected products [20]. The first
family consisted of geometrically differing polyamines described in
Fig. 1.4.
in vivo
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