Advancing Antiamyloidogenic Activity by Fine-Tuning Macromolecular Topology.

Amyloid ß peptide can aggregate into thin ß-sheet fibrils or plaques deposited on the extracellular matrix, which is the hallmark of Alzheimer's disease. Multifunctional macromolecular structures play an important role in inhibiting the aggregate formation of amyloidogenic materials and thus are promising candidates with antiamyloidogenic characteristics for the development of next-generation therapeutics. In this study, we evaluate how small differences in the dendritic topology of these structures influence their antiamyloidogenic activity by the comparison of "perfectly dendritic" and "pseudodendritic" macromolecules, both decorated with mannose units. Their compactness, the position of surface units, and the size of glyco-architectures influence their antiamyloidogenic activity against Aß 40, a major component of amyloid plaques. For the advanced analysis of the aggregation of the Aß peptide, we introduce asymmetric flow field flow fractionation as a suitable method for the quantification of large and delicate structures. This alternative method focuses on the quantification of complex aggregates of Aß 40 and glycodendrimer/glyco-pseudodendrimer over different time intervals of incubation, showing a good correlation to ThT assay and CD spectroscopy results. Kinetic studies of the second-generation glyco-pseudodendrimer revealed maximum inhibition of Aß 40 aggregates, verified with atomic force microscopy. The second-generation glyco-pseudodendrimer shows the best antiamyloidogenic properties confirming that macromolecular conformation in combination with optimal functional group distribution is the key to its performance. These molecular properties were validated and confirmed by molecular dynamics simulation.

Elucidating the Chemistry behind the Reduction of Graphene Oxide Using a Green Approach with Polydopamine.

A new approach using X-ray photoelectron spectroscopy (XPS) was employed to give insight into the reduction of graphene oxide (GO) using a green approach with polydopamine (PDA). In this approach, the number of carbon atoms bonded to OH and to nitrogen in PDA is considered and compared to the total intensity of the signal resulting from OH groups in polydopamine-reduced graphene oxide (PDA-GO) to show the reduction. For this purpose, GO and PDA-GO with different times of reduction were prepared and characterized by Raman Spectroscopy and XPS. The PDA layer was removed to prepare reduced graphene oxide (RGO) and the effect of all chemical treatments on the thermal and electrical properties of the materials was studied. The results show that the complete reduction of the OH groups in GO occurred after 180 min of reaction. It was also concluded that Raman spectroscopy is not well suited to determine if the reduction and restoration of the sp2 structure occurred. Moreover, a significant change in the thermal stability was not observed with the chemical treatments. Finally, the electrical powder conductivity decreased after reduction with PDA, increasing again after its removal.

Glyco-pseudodendrimers on a Polyester Basis: Synthesis and Investigation of Protein-Pseudodendrimer Interaction.

Molar mass and end group number of a hyperbranched polyester are significantly increased by its transformation to a pseudodendrimer. Three generations of pseudodendrimers are obtained from hyperbranched aliphatic polyester core by modification with a protected AB*2 monomer. A sequence of protection and deprotection steps leads to OH-terminated pseudodendrimers. NMR studies confirm maximum degree of branching in the first generation, which slightly decreases in the next two generations. Uniform, dense molecular structure formation was confirmed by MD simulation. Further modification to glyco-pseudodendrimers was performed with α-D-mannose leading to high molar masses and dense distribution of sugar units. The interaction of these sugar units with a plant lectin concanavalin A (Con A) was investigated using dynamic light scattering and cryogenic transmission electron microscopy. The protein-interaction studies of the glyco-pseudodendrimers confirm a loose network with Con A. The interaction activity depends on the generation number and modification degree.

Dendronized Hyperbranched Macromolecules: Soft Matter with a Novel Type of Segmental Distribution.

Dendronization of a hyperbranched polyester with different generation dendrons leads to pseudo-dendritic structures. The hyperbranched core is modified by the divergent coupling of protected monomer units to the functional groups. Compared to dendrimers, the synthetic effort is significantly less, but the properties are very close to those of high-generation dendrimers. The number of functional groups, molar mass, and rheology behavior even in the early generation (G1-G4) pseudo-dendrimers strongly resembles the behavior of dendrimers in higher generations (G5-G8). Comparison of the segmental and internal structure with perfect dendrimers is performed using SANS, dynamic light scattering and viscosity analysis, microscopy and molecular dynamics simulation. The interpretation of the results reveals unique structural characteristics arising from lower segmental density of the core, which turns into a soft nano-sphere with a smooth surface even in the first generation.

Formation of oligomeric and macrocyclic ureas based on 2,6-diaminopyridine.

The conversion of 1,3-bis-(6-amino-pyridin-2-yl)-urea (1) with N,N'-carbonyldiimidazole at high temperatures in DMSO yielded a mixture of defined cyclic trimers and tetramers. On the basis of model reactions, exchange reactions were evidenced, which convert the cyclic tetramer into a stable cyclic trimer. Linear even numbered oligomers were obtained in acetone under reflux where side reactions were suppressed. The pronounced tendency of cyclization is attributed to a preferred folded conformation of the urea bond between two pyridyl units.

Oligosaccharide-modified poly(propyleneimine) dendrimers: synthesis, structure determination, and Cu(II) complexation.

The multiple application of reductive amination on primary amino groups of first and second generation poly(propyleneimine) dendrimers is used as a one-pot approach to introduce twice the amount of the oligosaccharide units as surface groups, compared to initially present amino groups in the first and second generation dendrimers. This was proven by (1)H NMR, MALDI-TOF-MS, and LILBID-MS analysis. The size of these dendrimers was determined by the hydrodynamic radius using pulsed field gradient NMR and dynamic light scattering. Molecular modeling confirmed the presence of dense-shell dendrimers. These dendrimers exhibit a generation dependent Cu(II)/dendrimer ratio in an aqueous environment, highlighting these materials as possible metal-carrier systems with a well-defined oligosaccharide protection shell for application in a biological environment.