2 research outputs found
Stereochemical Effect Revealed in Self-Assemblies Based on Archaeal Lipid Analogues Bearing a Central Five-Membered Carbocycle: A SAXS Study
The relative stereochemistry (cis or trans) of a 1,3-disubstituted
cyclopentane unit in the middle of tetraether archaeal bipolar lipid
analogues was found to have a dramatic influence on their supramolecular
self-assembly properties. SAXS studies of two synthetic diastereomeric
archaeal lipids bearing two lactosyl polar head groups at opposite
ends revealed different lyotropic behaviors. The cis isomer led to
L<sub>c</sub>–L<sub>α</sub>–Q<sub>II</sub> transitions
whereas the trans isomer retained an L<sub>α</sub> phase from
20 to 100 °C. These main differences originate from the conformational
equilibrium (pseudorotation) of 1,3-disubstituted cyclopentanes. Indeed,
this pseudorotation exhibits quite similar orientations of the two
substituents in a trans isomer whereas several orientations of the
two alkyl chains are expected in a <i>cis</i>-1,3-dialkyl
cyclopentane, thus authorizing more conformational flexibility in
the lipid packing
Effects of a Novel Archaeal Tetraether-Based Colipid on the <i>In Vivo</i> Gene Transfer Activity of Two Cationic Amphiphiles
Gene therapy for treating inherited
diseases like cystic fibrosis
might be achieved using multimodular nonviral lipid-based systems.
To date, most optimizations have concerned cationic lipids rather
than colipids. In this study, an original archaeal tetraether derivative
was used as a colipid in combination with one or the other of two
monocationic amphiphiles. The liposomes obtained, termed archaeosomes,
were characterized regarding lipid self-assembling properties, macroscopic/microscopic
structures, DNA condensation/neutralization/relaxation abilities,
and colloidal stability in the presence of serum. In addition, gene
transfer experiments were conducted in mice with lipid/DNA complexes
being administered via systemic or local delivery routes. Altogether,
the results showed that the tetraether colipid can provide complexes
with different <i>in vivo</i> transfection abilities depending
on the lipid combination, the lipid/colipid molar ratio, and the administration
route. This original colipid appears thus as an innovative modular
platform endowed with properties possibly beneficial for fine-tuning
of <i>in vivo</i> lipofection and other biomedical applications