Chemistry Reference
In-Depth Information
selectively cleaved in some dendrimers. The important conclusion is the decreasing
ability of the enzymes to interact with the substrates as the branching degree increases.
It also seemed related to the rigidity of dendrimers and to the steric hindrance. Higher
generation dendrimers behave poorly as a function of the generation number.
As for poly(amides) or peptide dendrimers, a general trend is that branching causes
of a slower degradation. There is a case where a linear poly(
L
-glutamic acid) was
degraded faster than a cored-PAMAM poly(
L
-glutamic acid) dendrimer in the
presence of the protease cathepsin B [142]. Another example described a greater
difficulty for proteases to cleave dendrimers. Tetrabranched peptides were shown to
be more stable and even protease and peptidase resistant to degradation. Monomeric
versus tetrabranched dendrimeric mimotope peptides were tested for a degradation in
plasma, in serum or with trypsin and chymotrypsin [171]. Another report on
antimicrobial dendrimeric peptides demonstrated the greater proteolytic stability of
a dendrimeric structure compared to the linear tetra- or octapeptides in the presence of
trypsin or chymotrypsin [172].
From a very limited set of data, the following trends are a general guidelines for the
enzymatic degradation of some dendritic macromolecules of similar molecular
weights, linkages, and repetitive monomeric composition:
(a) A cleavage in the proximity of a branching point is slower compared to a
cleavage of a linear substrate because of steric effects.
(b) An open dendritic structure of low generation number or a dendron might be
cleaved faster than a higher generation dendrimer because of an easier access
to a catalytic site of an enzyme and a larger conformational flexibility.
(c) The rate of cleavage of an open structure of a low generation dendrimer might
be slower than for a linear polymer, depending on a conformational flexibility
and the hydrophilicity.
(d) Higher dendritic generations with a dense periphery in a close shell will be
cleaved very slowly because of serious steric effects and a high degree of
branching. A conformational flexibility is also limited.
(e) A star-shape dendrimer, which has an intermediate topology and conforma-
tional flexibility between a linear polymer and a low generation dendrimer
would behave in a borderline case, but cleavage will first occur faster on a
linear structure, distant from the branching core.
(f) As for proteases, a proteolytic cleavage is slower for peptide dendritic
structures, compared to peptide linear structures.
Further data and model dendrimers would be needed to assert those trends solely
based on a few experimental data. Other effects might overcome those factors,
especially the hydrophilic/lipophilic or hydrophobic interactions, causing some
important conformational issues in dendrimers and polymer chemistry.
13.2.3.5 Surface Functionalization In the recent years, the modern concepts of
“multifunctional dendrimers” or “multifunctional dendritic nanodevices” were
