7 research outputs found
Expedient Synthesis of Chiral Oxazolidinone Scaffolds via Rhodium-Catalyzed Asymmetric Ring-Opening with Sodium Cyanate
A method for synthesizing chiral oxazolidinone scaffolds from readily available oxabicyclic alkenes is described. The reaction utilizes a domino sequence of Rh(I)-catalyzed asymmetric ring-opening (ARO) with sodium cyanate as a novel nucleophile followed by intramolecular cyclization to generate oxazolidinone products in excellent enantioselectivities (<i>trans</i> stereochemistry)
Expedient Synthesis of Chiral Oxazolidinone Scaffolds via Rhodium-Catalyzed Asymmetric Ring-Opening with Sodium Cyanate
A method for synthesizing chiral oxazolidinone scaffolds from readily available oxabicyclic alkenes is described. The reaction utilizes a domino sequence of Rh(I)-catalyzed asymmetric ring-opening (ARO) with sodium cyanate as a novel nucleophile followed by intramolecular cyclization to generate oxazolidinone products in excellent enantioselectivities (<i>trans</i> stereochemistry)
Exploiting Oligo(amido amine) Backbones for the Multivalent Presentation of Coiled-Coil Peptides
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
oligoÂ(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 oligoÂ(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
Exploiting Oligo(amido amine) Backbones for the Multivalent Presentation of Coiled-Coil Peptides
The
investigation of coiled coil formation for one mono- and two
divalent peptideâpolymer conjugates is presented. Through the
assembly of the full conjugates on solid support, monodisperse sequence-defined
conjugates are obtained with defined positions and distances between
the peptide side chains along the polymeric backbone. A heteromeric
peptide design was chosen, where peptide K is attached to the polymer
backbone, and coiled-coil formation is only expected through complexation
with the complementary peptide E. Indeed, the monovalent peptide K-polymer
conjugate displays rapid coiled-coil formation when mixed with the
complementary peptide E sequence. The divalent systems show intramolecular
homomeric coiled-coil formation on the polymer backbone despite the
peptide design. Interestingly, this intramolecular assembly undergoes
a conformational rearrangement by the addition of the complementary
peptide E leading to the formation of heteromeric coiled coilâpolymer
aggregates. The polymer backbone acts as a template bringing the covalently
bound peptide strands in close proximity to each other, increasing
the local concentration and inducing the otherwise nonfavorable formation
of intramolecular helical assemblies
Carbohydrate-Lectin Recognition of Sequence-Defined Heteromultivalent Glycooligomers
Multivalency as a key principle in
nature has been successfully
adopted for the design and synthesis of artificial glycoligands by
attaching multiple copies of monosaccharides to a synthetic scaffold.
Besides their potential in various applied areas, e.g. as antiviral
drugs, for the vaccine development and as novel biosensors, such glycomimetics
also allow for a deeper understanding of the fundamental aspects of
multivalent binding of both artificial and natural ligands. However,
most glycomimetics so far neglect the purposeful arranged heterogeneity
of their natural counterparts, thus limiting more detailed insights
into the design and synthesis of novel glycomimetics. Therefore, this
work presents the synthesis of monodisperse glycooligomers carrying
different sugar ligands at well-defined positions along the backbone
using for the first time sequential click chemistry and stepwise assembly
of functional building blocks on solid support. This approach allows
for straightforward access to sequence-defined, multivalent glycooligomers
with full control over number, spacing, position, and type of sugar
ligand. We demonstrate the synthesis of a set of heteromultivalent
oligomers presenting mannose, galactose, and glucose residues. All
heteromultivalent structures show surprisingly high affinities toward
Concanavalin A lectin receptor in comparison to their homomultivalent
analogues presenting the same number of binding ligands. Detailed
studies of the ligand/receptor interaction using STD-NMR and 2fFCS
indeed indicate a change in binding mechanism for trivalent glycooligomers
presenting mannose or combinations of mannose and galactose residues.
We find that galactose residues do not participate in the binding
to the receptor, but they promote steric shielding of the heteromultivalent
glycoligands and thus result in an overall increase in affinity. Furthermore,
the introduction of nonbinding ligands seems to suppress receptor
clustering of multivalent ligands. Overall these results support the
importance of heteromultivalency specifically for the design of novel
glycoligands and help to promote a fundamental understanding of multivalent
binding modes