Efficient Cleavage of pUC19 DNA by Tetraaminonaphthols.

In an attempt to create models of phosphodiesterases, we previously investigated bis(guanidinium) naphthols. Such metal-free anion receptors cleaved aryl phosphates and also plasmid DNA. Observed reaction rates, however, could not compete with those of highly reactive metal complexes.

Redirection of miRNA-Argonaute Complexes to Specific Target Sites by Synthetic Adaptor Molecules.

Dysregulation of miRNAs is connected with a multitude of diseases for which antagomirs and miRNA replacement are discussed as therapeutic options. Here, we suggest an alternative concept based on the redirection of RISCs to non-native target sites. Metabolically stable DNA-LNA mixmers are used to mediate the binding of RISCs to mRNAs without any direct base complementarity to the presented guide RNA strand.

Peptidomimetics That Inhibit and Partially Reverse the Aggregation of Aβ.

The peptide sequence KLVFF resembles the hydrophobic core of the Aβ peptide known to form amyloid plaques in Alzheimer's disease. Starting from its retro-inverso peptide, we have synthesized three generations of peptidomimetics. Step by step natural amino acids have been replaced by aromatic building blocks accessible from the Pd-catalyzed Catellani reaction.

Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial ribonuclease tris(2-aminobenzimidazole).

Tris(2-aminobenzimidazole) conjugates with antisense oligonucleotides are effective site-specific RNA cleavers. Their mechanism of action is independent of metal ions. Here we investigate conjugates with peptide nucleic acids (PNA).

Fragment based search for small molecule inhibitors of HIV-1 Tat-TAR.

Basic molecular building blocks such as benzene rings, amidines, guanidines, and amino groups have been combined in a systematic way to generate ligand candidates for HIV-1 TAR RNA. Ranking of the resulting compounds was achieved in a fluorimetric Tat-TAR competition assay. Although simple molecules such as phenylguanidine are inactive, few iteration steps led to a set of ligands with IC50 values ranging from 40 to 150 μM.

Laser-induced liquid bead ion desorption mass spectrometry: an approach to precisely monitor the oligomerization of the β-amyloid peptide.

In the present work, the recently developed laser-induced liquid bead ion desorption mass spectrometry (LILBID MS) is applied as a novel technique to study Aβ oligomerization, thought to be crucial in Alzheimer's disease (AD). The characterization of the earliest nucleation events of this peptide necessitates the application of several techniques to bridge the gap between small oligomers and large fibrils. We precisely monitored in time the transformation of monomeric Aβ (1-42) into oligomeric Aβ(n) (n < 20) and its dependence on concentration and agitation.

Metal-free catalysts for the hydrolysis of RNA derived from guanidines, 2-aminopyridines, and 2-aminobenzimidazoles.

2-aminopyridine and 2-aminobenzimidazole were chosen as structural analogues to substitute guanidinium groups in receptor molecules designed as phosphoryl transfer catalysts. Shifting the pKa of the guanidinium analogues toward 7 was expected to raise catalytic activities in aqueous buffer. Although the pKa's of both heterocycles are similar (6.