Gene/Protein Disease Symptom Drug Enzyme Compound
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Memantine (Namenda) is prescribed as a treatment for moderate to severe Alzheimer's Disease. Memantine functions by blocking the NMDA receptor, but the key binding interactions between drug and receptor are not fully elucidated. To determine key binding interactions of memantine, we made side-by-side comparisons of IC(50) for memantine and amantadine, a structurally related drug, in the GluN1/GluN2B NMDA receptor. We identified hydrophobic binding pockets for the two methyl groups on memantine formed by the residues A645 and A644 on the third transmembrane helices of GluN1 and GluN2B, respectively. Moreover, we found that while adding two methyl groups to amantadine to produce memantine greatly improves affinity, adding a third methyl group to produce the symmetrical trimethylamantadine diminished affinity. Our results provide a better understanding of chemical-scale interactions between memantine and the NMDA channel, which will potentially benefit the development of new drugs for neurodegenerative diseases involving NMDA receptors.
ACS Chem Neurosci 2013 Feb 20
PMID:Key binding interactions for memantine in the NMDA receptor. 2342 76

Novel opal hydrogels with water-tunable photonic bandgap (PBG) exhibiting responses to external stimuli were self-assembled from polystyrene-co-poly(N,N-dimethylacrylamide) (PS-co-PDMAA) microspheres. The polymeric microspheres with narrow size distribution were successfully prepared in water, consisting of two regions. The inner region is rich in PS which is hard and hydrophobic; the outer region is rich in PDMAA which is soft and hydrophilic. The self-assembly of the PS-co-PDMAA hydrogel microspheres is ready induced by centrifugation and resulted in highly ordered three-dimensional (3D) photonic colloidal crystals (PCCs). With an increase of the amount of water, the PBG of the opal hydrogels shifted from the visible to near-infrared region of the electromagnetic spectrum. The maximum shift of diffraction peak positions could be larger than 500 nm with narrow full width at half maximum (FWHM) in the range of 20 to 40 nm only. The change in color was visible to the naked eye. The remarkable sensitivity to water of the lattice spacing of the opal hydrogels was repeatable after centrifugation. These observations are attributed to a reproducible degree of hydration of the hydrophilic outer region of the polymeric microspheres. Furthermore, the diffraction of the opal hydrogels was particularly sensitive to the presence of thiocyanate (SCN(-)) ions. The interaction between SCN(-) ions and DMAA repeat units is argued to block hydrogen bonds between DMAA and water molecules. Our PS-co-PDMAA opal hydrogels could be a practical system for diffraction-based detections.
ACS Appl Mater Interfaces 2013 Mar
PMID:Centrifugation-induced water-tunable photonic colloidal crystals with narrow diffraction bandwidth and highly sensitive detection of SCN-. 2344 68

Combining the stability of solid-state nanopores with the unique sensing properties of biological components in a miniaturized electrical hybrid nanopore device is a challenging approach to advance the sensitivity and selectivity of small-molecule detection in healthcare and environment analytics. Here, we demonstrate a simple method to design an electrical hybrid nanosensor comprising a bacterial binding protein tethered to a solid-state nanopore allowing high-affinity detection of phosphonates. The diverse family of bacterial substrate-binding proteins (SBPs) binds specifically and efficiently to various substances and has been implicated as an ideal biorecognition element for analyte detection in the design of hybrid bionanosensors. Here, we demonstrate that the coupling of the purified phosphonate binding protein PhnD via primary amines to the reactive NHS groups of P(DMAA-co-NMAS) polymers inside a single track-etched nanopore in poly(ethylene terephthalate) (PET) foils results in ligand-specific and concentration-dependent changes in the nanopore current. Application of the phosphonate 2-aminoethylphosphonate (2AEP) or ethylphosphonate (EP) induces a large conformational rearrangement in PnhD around the hinge in a venus flytrap mechanism resulting in a concentration depended on increase of the single pore current with binding affinities of 27 and 373 nM, respectively. Thus, the specificity and stability of this simple hybrid sensor concept combine the advantages of both, the diversity of ligand-specific substrate-binding proteins and solid-state nanopores encouraging further options to produce robust devices amenable to medical or environmental high-throughput-based applications in nanotechnology.
ACS Sens 2020 01 24
PMID:Electrical Sensing of Phosphonates by Functional Coupling of Phosphonate Binding Protein PhnD to Solid-State Nanopores. 3182 17