Biomedical Engineering Reference
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form complexes with DNA similarly to those obtained with non-
degradable polycationic systems. After penetration into the cell
the disulfide bridges are progressively degraded by the reducing
conditions found at the different cytosolic compartments, inducing
the release of DNA from complexes. The polymer is finally degraded
to nontoxic monomers or peptides, and DNA is released for
transfection.
Building block
was synthesized and introduced along the
peptide chains of various polypeptides using conventional SPPS (see
Fig. 1.15).
SSa
SSa
=
Fmoc-NHCH
CH
-S-S-CH
CH
NHCOCH
CH
COOH
2
2
2
2
2
2
Lys
n
n
= 1, 2, 3
H-(K
SSa
)
K
NH
10
n
10
2
His
n
n
= 1, 2
H-(H
SSa
)
H
NH
10
n
10
2
Figure 1.1
Reduction sensitive cationic polypeptides synthesized using
building block
SSa.
In another approach, we have developed a new method for solid-
phase inter-site disulfide bond formation that resulted in dimers
containing cysteine bridges. These dimers were generated after
conventional SPPS of the polypeptides containing (S-trityl)cysteine
at different positions. The cysteine residues were bridged on the
solid support using iodine in methanol (see Fig. 1.16).
H -A A
m
C y[A A ]
n
N H
2
A A
m
C y[A A (B o c )]
n
A A
m
C y[A A (B o c )]
n
A A
m
C ys (trityl)[A A (B o c )]
n
T F A
I
2
/M e O H
A A
m
C ys (trityl)[A A (B o c )]
n
H -A A
m
C y[A A ]
n
N H
2
Figure 1.1
Reduction-sensitive cationic polypeptides obtained by solid-
phase inter-site disulfide bridge formation: AA = K (
CyK
,
m
= 0,
n
= 10;
KcyK
,
m
= 8,
n
= 2); H (
CyH
,
m
= 0,
n
= 10;
HCyH
,
m
= 8,
n
= 2); R (
CyR
,
m
= 0,
n
= 10).
Additionally, we have combined the use of building block SSa
and the inter-site disulfide bridge formation to obtain the long
cationic polypeptide containing 40 histidines, FIM-2256: (H-H
-
10
SSa
.
Finally, we have synthesized the dendrimer FIM-2126 that
contains a disulfide bridge (see Fig. 1.17).
-
Cy
-H
NH
)
10
2
2
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