3 research outputs found
Mechanical Compressibility of the Glycosylphosphatidylinositol (GPI) Anchor Backbone Governed by Independent Glycosidic Linkages
About 1% of the human proteome is anchored to the outer
leaflet
of cell membranes via a class of glycolipids called GPI anchors. In
spite of their ubiquity, experimental information about the conformational
dynamics of these glycolipids is rather limited. Here, we use a variety
of computer simulation techniques to elucidate the conformational
flexibility of the Man-α(1→2)-Man-α(1→6)-Man-α(1→4)-GlcNAc-α-OMe
tetrasaccharide backbone <b>2</b> that is an essential and invariant
part of all GPI-anchors. In addition to the complete tetrasaccharide
structure, all disaccharide and trisaccharide subunits of the GPI
backbone have been studied as independent moieties. The extended free
energy landscape as a function of the corresponding dihedral angles
has been determined for each glycosidic linkage relevant for the conformational
preferences of the tetrasaccharide backbone (Man-α(1→2)-Man,
Man-α(1→6)Man and Man-α(1→4)-GlcNAc). We
compared the free energy landscapes obtained for the same glycosidic
linkage within different oligosaccharides. This comparison reveals
that the conformational properties of a linkage are primarily determined
by its two connecting carbohydrate moieties, just as in the corresponding
disaccharide. Furthermore, we can show that the torsions of the different
glycosidic linkages within the GPI tetrasaccharide can be considered
as statistically independent degrees of freedom. Using this insight,
we are able to map the atomistic description to an effective, reduced
model and study the response of the tetrasaccharide <b>2</b> to external forces. Even though the backbone assumes essentially
a single, extended conformation in the absence of mechanical stress,
it can be easily bent by forces of physiological magnitude
Triazoles: A New Class of Precursors for the Synthesis of Negatively Charged Carbon Nitride Derivatives
Carbon nitride polymers were prepared
for the first time by the
pyrolysis of 3,5-disubstituted-1,2,4-triazole derivatives, namely,
3,5-diamino-1,2,4-triazole [<b>1</b>] and 3-amino-1,2,4-triazole-5-thiol
[<b>2</b>], in bulk as well as in LiCl/KCl salt melts. The reaction
of [<b>1</b>] and [<b>2</b>] in bulk yields condensed
heptazine-based polymers, while in LiCl/KCl eutectics it leads to
the formation of well-defined potassium poly(heptazine imides), according
to the results of <sup>13</sup>C NMR and XPS investigations, whose
formation resembles that of emeraldine salts of polyaniline. The density
functional calculations supported the structural model suggested for
potassium poly(heptazine imide) polymer. Owing to the specific reaction
path, the products obtained from triazoles therefore show electronic
properties rather different to known carbon nitrides, such as band
gap and conduction and valence bands positions. With the degree of
crystallinity of the reference materials, triazole-derived carbon
nitrides are characterized by almost complete absence of steady photoluminescence,
since charge separation and delocalization upon excitation seem to
be improved. As a consequence, photocatalysts prepared from [<b>2</b>] outperform classical carbon nitrides in a model dye degradation
reaction and mesoporous graphitic carbon nitride in hydrogen evolution
reaction under visible light irradiation. On its turn, [<b>1</b>] can be conveniently used as a comonomer in order to prepare carbon
nitrides with improved visible light absorption
Photosensitive Peptidomimetic for Light-Controlled, Reversible DNA Compaction
Light-induced
DNA compaction as part of nonviral gene delivery
was investigated intensively in the past years, although the bridging
between the artificial light switchable compacting agents and biocompatible
light insensitive compacting agents was not achieved until now. In
this paper, we report on light-induced compaction and decompaction
of DNA molecules in the presence of a new type of agent, a multivalent
cationic peptidomimetic molecule containing a photosensitive Azo-group
as a branch (Azo-PM). Azo-PM is synthesized using a solid-phase procedure
during which an azobenzene unit is attached as a side chain to an
oligo(amidoamine) backbone. We show that within a certain range of
concentrations and under illumination with light of appropriate wavelengths,
these cationic molecules induce reversible DNA compaction/decompaction
by photoisomerization of the incorporated azobenzene unit between
a hydrophobic <i>trans</i>- and a hydrophilic <i>cis</i>-conformation, as characterized by dynamic light scattering and AFM
measurements. In contrast to other molecular species used for invasive
DNA compaction, such as widely used azobenzene containing cationic
surfactant (Azo-TAB, C<sub>4</sub>-Azo-OC<sub>X</sub>-TMAB), the presented
peptidomimetic agent appears to lead to different complexation/compaction
mechanisms. An investigation of Azo-PM in close proximity to a DNA
segment by means of a molecular dynamics simulation sustains a picture
in which Azo-PM acts as a multivalent counterion, with its rather
large cationic oligo(amidoamine) backbone dominating the interaction
with the double helix, fine-tuned or assisted by the presence and
isomerization state of the Azo-moiety. However, due to its peptidomimetic
backbone, Azo-PM should be far less toxic than photosensitive surfactants
and might represent a starting point for a conscious design of photoswitchable,
biocompatible vectors for gene delivery