and of an alginate rich in a-L-guluronate units. These authors concluded that the
conformation of this ALG form is too stiff (twofold helix) and can interact neither
with PLL nor with PDL effectively due to a lack of charge matching. Whereas this
pectate form exhibits more conformational freedom, both twofold and threefold
helices are possible and thus it allows better charge matching. However, this was
only found for pectate/PLL and not for pectate/PDL. Therefore, the handedness of
the polysaccharide was claimed to also have an influence and the authors finally
concluded that PLL shows both a-helical induction and complexation with right
handed anionic polysaccharides, whereas PDL shows a-helical induction and
complexation with left-handed polysaccharides.
Such model interaction studies will find a certain “renaissance” in the framework
of the interaction between anionic polysaccharides constituting the extracellular
matrix (ECM) and proteinogenic growth factors (cytokines), which is highly
relevant for research on angiogenesis (vascularization) and tissue engineering.
Recently, Petitou and coworkers [95] reported molecular modeling work on the
specific interaction between heparan sulfate and cellular growth factors,
emphasizing the plasticity of their interaction at a molecular scale. Also related to
this topic is a report by Pisabarro and coworkers [96], who used fluorescence and
computational methods to study the interaction between interleukin-8 (IL-8) and
glycosaminoglycans of the ECM and their derivatives with defined sulfation
degrees. They found that the sulfation pattern determines the binding strength, so
that generally increasing the sulfation degree resulted in enhanced binding. Furthermore, in the case of equal sulfation degree, the sulfate substitution position is
also important. The analysis revealed a tetrasaccharide as the minimum glycosaminoglycan unit necessary to obtain specific binding to IL-8.
Influence of pH
It is well known that uncomplexed PLL at pH ¼ 10 is nearly uncharged (pK a % 10)
and adopts the a-helical conformation [97] without any polyanion complexation.
Hence, PEC particles of PLL and sodium polymethacrylate (PMAC) were prepared
at pH ¼ 6/6 (PLL/PAC) and at pH ¼ 10/10 to study the influence of pH on the
conformation of PLL in the complexed state. It was found that even for complexes
of PLL with a-helix-breaking polyanions, the PLL conformation was always
a-helical when the complex was formed at pH ¼ 10/10. In Fig. 25, typical CD
spectra for PEC particles consisting of PLL and PMAC formed at pH ¼ 6/6 and at
pH ¼ 10/10 are shown [98].
The typical negative peak at around 195 nm of the randomly coiled/extended
chain was observed for pH ¼ 6/6 (PLL/PMAC), whereas the diagnostic doublet at
208 and 225 nm of the a-helix was observed for pH ¼ 10/10. Obviously, at
pH ¼ 10/10 the PLL in PLL/PMAC complex particles shows the a-helical conformation. Two arguments can be raised: first, PLL at pH ¼ 10 adopts an a-helical
conformation, which does not change upon complexation with PMAC; and second,
PMAC at pH ¼ 10 is fully ionized and is expected to adopt an extended
Sizing, Shaping and Pharmaceutical Applications of Polyelectrolyte Complex. . .
229
conformation of this ALG form is too stiff (twofold helix) and can interact neither
with PLL nor with PDL effectively due to a lack of charge matching. Whereas this
pectate form exhibits more conformational freedom, both twofold and threefold
helices are possible and thus it allows better charge matching. However, this was
only found for pectate/PLL and not for pectate/PDL. Therefore, the handedness of
the polysaccharide was claimed to also have an influence and the authors finally
concluded that PLL shows both a-helical induction and complexation with right
handed anionic polysaccharides, whereas PDL shows a-helical induction and
complexation with left-handed polysaccharides.
Such model interaction studies will find a certain “renaissance” in the framework
of the interaction between anionic polysaccharides constituting the extracellular
matrix (ECM) and proteinogenic growth factors (cytokines), which is highly
relevant for research on angiogenesis (vascularization) and tissue engineering.
Recently, Petitou and coworkers [95] reported molecular modeling work on the
specific interaction between heparan sulfate and cellular growth factors,
emphasizing the plasticity of their interaction at a molecular scale. Also related to
this topic is a report by Pisabarro and coworkers [96], who used fluorescence and
computational methods to study the interaction between interleukin-8 (IL-8) and
glycosaminoglycans of the ECM and their derivatives with defined sulfation
degrees. They found that the sulfation pattern determines the binding strength, so
that generally increasing the sulfation degree resulted in enhanced binding. Furthermore, in the case of equal sulfation degree, the sulfate substitution position is
also important. The analysis revealed a tetrasaccharide as the minimum glycosaminoglycan unit necessary to obtain specific binding to IL-8.
Influence of pH
It is well known that uncomplexed PLL at pH ¼ 10 is nearly uncharged (pK a % 10)
and adopts the a-helical conformation [97] without any polyanion complexation.
Hence, PEC particles of PLL and sodium polymethacrylate (PMAC) were prepared
at pH ¼ 6/6 (PLL/PAC) and at pH ¼ 10/10 to study the influence of pH on the
conformation of PLL in the complexed state. It was found that even for complexes
of PLL with a-helix-breaking polyanions, the PLL conformation was always
a-helical when the complex was formed at pH ¼ 10/10. In Fig. 25, typical CD
spectra for PEC particles consisting of PLL and PMAC formed at pH ¼ 6/6 and at
pH ¼ 10/10 are shown [98].
The typical negative peak at around 195 nm of the randomly coiled/extended
chain was observed for pH ¼ 6/6 (PLL/PMAC), whereas the diagnostic doublet at
208 and 225 nm of the a-helix was observed for pH ¼ 10/10. Obviously, at
pH ¼ 10/10 the PLL in PLL/PMAC complex particles shows the a-helical conformation. Two arguments can be raised: first, PLL at pH ¼ 10 adopts an a-helical
conformation, which does not change upon complexation with PMAC; and second,
PMAC at pH ¼ 10 is fully ionized and is expected to adopt an extended
Sizing, Shaping and Pharmaceutical Applications of Polyelectrolyte Complex. . .
229