Biomedical Engineering Reference
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H
N
H
H
O
R1
H
H
R1
O
H
H
N
H
H
H
O
N
N
N
N
N
N
H
R1
R1
5
NH
6
O
R1
H
2
N
N
R1
a
a, b
H
O
O
H
H
boc
N
H
O
S
N
R1
H
O
H
2
N
N
R1
N
NH
H
2
N
1.2 eq.
symbol
5
6
7
8
R1
n
1
1
2
2
[CH
2
]n
(CH
2
)
13
CH
3
(CH
2
)
13
CH
3
(CH
2
)
13
CH
3
(CH
2
)
17
CH
3
NH
2
N
boc
a, b
N
boc
O
H
O
N
N
R1
R1
H
O
R1
H
H
N
N
N
H
R1
NH
O
7-8
Figure 1.11
Synthesis of lipopolyamino-cycloguanidines. (a) dichlo-
romethane, TEA (1,3 eq), 20°C, overnight, HPLC purification.
(b) TFA/DCM (1:1) 1 h 20°C (see Ref. [33] for detailed experi-
mental procedure).
1..1 Biodegradable Lipoplexes:
Reduction-Sensitive Lipopolyamines
We have designed and synthesized original lipopolyamines for
modulated release of DNA from cationic lipid/DNA complexes [22,
34-36]. Our rationale was that modulated degradation of the lipids
during or after penetration into the cell could improve the trafficking
of DNA to the nucleus, resulting in increased transgene expression.
The new reduction-sensitive lipopolyamines (RSL) harbor a disulfide
bridge within different positions in the backbone of the lipids as
bio-sensitive function. A useful synthetic method was developed to
obtain unsymmetrical disulfide bridged molecules with very good
yields and reproducibility, starting from symmetrical disulfides
and thiols [22]. The new lipopolyamines are good candidates as
carriers of therapeutic genes for
gene delivery. To optimize
the transfection efficiency in these novel series, we have carried
in vivo
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