RNA-catalyzed evolution of catalytic RNA.

An RNA polymerase ribozyme that was obtained by directed evolution can propagate a functional RNA through repeated rounds of replication and selection, thereby enabling Darwinian evolution. Earlier versions of the polymerase did not have sufficient copying fidelity to propagate functional information, but a new variant with improved fidelity can replicate the hammerhead ribozyme through reciprocal synthesis of both the hammerhead and its complement, with the products then being selected for RNA-cleavage activity. Two evolutionary lineages were carried out in parallel, using either the prior low-fidelity or the newer high-fidelity polymerase.

Vitamin-guanosine monophosphate conjugates for in vitro transcription priming.

Expanding the catalytic repertoire of ribozymes to include vitamin synthesis requires efficient labelling of RNA with the substrate of interest, prior to in vitro selection. For this purpose, we rationally designed and synthesized six GMP-conjugates carrying a synthetic pre-thiamine or biotin precursor and investigated their transcription incorporation properties by T7 RNA polymerase.

Oligonucleotide promoted peptide bond formation using a tRNA mimicking approach.

TransferRNA's role in protein translation is the prime example of an Informational Leaving Group (ILG). A simplified model produced oligophenylalanine with a modified uracil as an ILG in the presence of specific oligonucleotides. Our preliminary studies contribute to the importance of hybrid species in bridging the gap between peptides and nucleic acids.

Enhancing activity and selectivity in a series of pyrrol-1-yl-1-hydroxypyrazole-based aldose reductase inhibitors: The case of trifluoroacetylation.

Aldose reductase (ALR2) has been the target of therapeutic intervention for over 40 years; first, for its role in long-term diabetic complications and more recently as a key mediator in inflammation and cancer. However, efforts to prepare small-molecule aldose reductase inhibitors (ARIs) have mostly yielded carboxylic acids with rather poor pharmacokinetics. To address this limitation, the 1-hydroxypyrazole moiety has been previously established as a bioisostere of acetic acid in a group of aroyl-substituted pyrrolyl derivatives.

N-substituted pyrrole-based scaffolds as potential anticancer and antiviral lead structures.

Undoubtedly, efficient cancer treatment has been a significant challenge for the scientific community over the last decades. Despite tremendous progress made towards this direction, there are still efforts needed to discover new anticancer drugs. In this work, a series of N-substituted pyrrolebased scaffolds have been synthesized and evaluated for antiproliferative activity against a panel of cancer cell lines (L1210, CEM and HeLa).