10 research outputs found
Synthesis of an Unlocked Nucleic Acid Terpyridine Monomer and Binding of Divalent Metal Ion in Nucleic Acid Duplexes
Reprint of âElectrochemical intercalator binding to single- and double-strand DNA- and LNA-based molecules on Au(111)-electrode surfacesâ
Electrochemical intercalator binding to single- and double-strand DNA- and LNA-based molecules on Au(111)-electrode surfaces
Polycation Induced Potential Dependent Structural Transitions of Oligonucleotide Monolayers on Au(111)-Surfaces
We have studied self-assembled molecular monolayers (SAMs)
of several
3â˛-C3-SH conjugated single-strand (ss) and double-strand (ds)
20-base oligonucleotides (ONs) immobilized on single-crystal, atomically
planar Au(111)-electrode surfaces in the presence of the triply positively
charged base spermidine (Spd). This cation binds strongly to the polyanionic
ON backbone and stabilizes the ds-form relative to the ss-form. A
combination of chemical ON synthesis, melting temperature measurements,
cyclic voltammetry (CV), and <i>in situ</i> scanning tunneling
microscopy (STM) in aqueous biological buffer under electrochemical
potential control was used. Spd binding was found to increase notably
the ds-ON melting temperature. CV displays capacitive features associated
with ss- and ds-ON. A robust capacitive peak around â0.35 V
versus saturated calomel electrode (SCE), specific to ds-ON and highly
sensitive to base pair mismatches, was consistently observed. The
peak is likely to be caused by surface structural reorganization around
the peak potential and located close to reported peak potentials of
several DNA intercalating or covalently tethered redox molecules reported
as probes for long-range electron transfer
StructureâActivity Study of Dihydrocinnamic Acids and Discovery of the Potent FFA1 (GPR40) Agonist TUG-469
[Image: see text] The free fatty acid 1 receptor (FFA1 or GPR40), which is highly expressed on pancreatic β-cells and amplifies glucose-stimulated insulin secretion, has emerged as an attractive target for the treatment of type 2 diabetes. Several FFA1 agonists containing the para-substituted dihydrocinnamic acid moiety are known. We here present a structureâactivity relationship study of this compound family suggesting that the central methyleneoxy linker is preferable for the smaller compounds, whereas the central methyleneamine linker gives higher potency to the larger compounds. The study resulted in the discovery of the potent and selective full FFA1 agonist TUG-469 (29)