Design of a functional protein for molecular recognition: specificity of ligand binding in a metal-assembled protein cavity probed by 19f NMR

A metal-assembled homotrimeric coiled coil based on the GCN4-p1 sequence has been designed that noncovalently binds hexafluorobenzene and other similar ligands in a hydrophobic cavity, created by making the core substitution Asn16Ala ([Fe(bpyGCN4-N16A)3]2+). The KD of binding of hexafluorobenzene with [Fe(bpyGCN4-N16A)3]2+ was observed to be 1.1(9) x 10(-4) M by diffusion NMR experiments. A control coiled coil with the core substitution Asn16Val ([Fe(bpyGCN4-N16V)3]2+) exhibited a significantly weaker association with hexafluorobenzene, providing evidence that even in the absence of structural data, benzene-like ligands bind in the cavity created by the Asn16Ala substitution. 19F NMR was employed to observe hexafluorobenzene binding and to monitor titrations with competing hydrophobic and polar ligands similar in size and shape to hexafluorobenzene. All hydrophobic ligands bound with greater affinity than the polar ligands in the hydrophobic core, although the cavity seems to be somewhat flexible in terms of the sizes of molecules it can accommodate. Thus 19F NMR has proved to be a useful spectral tool to probe molecular recognition in a hydrophobic cavity of a metal-assembled coiled coil.     

Multiple synaptic and membrane sites of anesthetic action in the CA1 region of rat hippocampal slices

Background  

Anesthesia is produced by a depression of central nervous system function, however, the sites and mechanisms of action underlying this depression remain poorly defined. The present study compared and contrasted effects produced by five general anesthetics on synaptic circuitry in the CA1 region of hippocampal slices.     

Modular diphosphine ligands based on bisphenol A backbones

A straightforward two-step synthesis is used to obtain new phosphorus-containing ligands based on readily available bisphenol A type backbones. Five diphosphine ligands have been prepared in good yields. An X-ray crystallographic study is presented for ligand 5. Preliminary results on rhodium-catalyzed hydroformylation exemplify the use of these ligands for homogeneous catalysis.     

Broadband phase noise suppression in a Yb-fiber frequency comb

We report a simple technique to suppress high-frequency phase noise of a Yb-based fiber optical frequency comb using an active intensity noise servo. Out-of-loop measurements of the phase noise using an optical heterodyne beat with a cw laser show suppression of phase noise by ≥7?dB out to Fourier frequencies of 100?kHz with a unity-gain crossing of ～700?kHz. These results are enabled by the strong correlation between the intensity and phase noise of the laser. Detailed measurements of intensity and phase noise spectra, as well as transfer functions, reveal that the dominant phase and intensity noise contribution above ～100?kHz is due to amplified spontaneous emission or other quantum noise sources.     

Scale and modify for the second and third order BDF methods

This paper investigates a ‘scale and modify’ technique used with variable stepsize BDF methods. When the stepsize is changed using the usual scaling procedure for Nordsieck methods, there can be adverse affects on the stability unless a severe restriction is placed on the allowable stepsize ratios. However, a modification to this scaling procedure may extend the range of permissible stepsize ratios. Results for the Nordsieck form of the second and third order methods indicate that this may be possible.