Cobalt(III)-Catalyzed C-H Amidation of Dehydroalanine for the Site-Selective Structural Diversification of Thiostrepton.

Thiostrepton is a potent antibiotic against a broad range of Gram-positive bacteria, but its medical applications have been limited by its poor aqueous solubility. In this work, the first C(sp )-H amidation of dehydroalanine (Dha) residues was applied to the site selective modification of thiostrepton to prepare a variety of derivatives. Unlike all prior methods for the modification of thiostrepton, the alkene framework of the Dha residue is preserved and with complete selectivity for the Z-stereoisomer.

Diversity of Secondary Structure in Catalytic Peptides with β-Turn-Biased Sequences.

X-ray crystallography has been applied to the structural analysis of a series of tetrapeptides that were previously assessed for catalytic activity in an atroposelective bromination reaction. Common to the series is a central Pro-Xaa sequence, where Pro is either l- or d-proline, which was chosen to favor nucleation of canonical β-turn secondary structures. Crystallographic analysis of 35 different peptide sequences revealed a range of conformational states.

Structural basis for DNA cleavage by the potent antiproliferative agent (-)-lomaiviticin A.

(-)-Lomaiviticin A (1) is a complex antiproliferative metabolite that inhibits the growth of many cultured cancer cell lines at low nanomolar-picomolar concentrations. (-)-Lomaiviticin A (1) possesses a C2-symmetric structure that contains two unusual diazotetrahydrobenzo[b]fluorene (diazofluorene) functional groups. Nucleophilic activation of each diazofluorene within 1 produces vinyl radical intermediates that affect hydrogen atom abstraction from DNA, leading to the formation of DNA double-strand breaks (DSBs).

Study of an S = 1 Ni(II) pincer electrocatalyst precursor for aqueous hydrogen production based on paramagnetic 1H NMR.

A tridentate NNN Ni(II) complex, shown to be an electrocatalyst for aqueous H2 production at low overpotentials, is studied by using temperature-dependent paramagnetic (1)H NMR. The NMR T1 relaxation rates, temperature dependence of the chemical shifts, and dc SQUID magnetic susceptibility are correlated to DFT chemical shifts and compared with the properties of a diamagnetic Zn analogue complex. The resulting characterization provides an unambiguous assignment of the six proton environments in the meridionally coordinating tridentate NNN ligand.

Green tea catechin, epigallocatechin-3-gallate, inhibits vascular endothelial growth factor angiogenic signaling by disrupting the formation of a receptor complex.

A potential mechanism by which green tea may prevent cancer development is through the inhibition of angiogenesis. We have shown previously that the green tea catechin, epigallocatechin gallate (EGCG), inhibits endothelial cell tube formation through the inhibition of vascular endothelial growth factor (VEGF)-induced Akt activation and vascular endothelial (VE)-cadherin phosphorylation. Furthermore, EGCG can suppress oxidant-induced production of the proangiogenic cytokine interleukin (IL)-8.

1H-15N correlation spectroscopy of nanocrystalline proteins.

The limits of resolution that can be obtained in 1H-15N 2D NMR spectroscopy of isotopically enriched nanocrystalline proteins are explored. Combinations of frequency switched Lee-Goldburg (FSLG) decoupling, fast magic angle sample spinning (MAS), and isotopic dilution via deuteration are investigated as methods for narrowing the amide 1H resonances. Heteronuclear decoupling of 15N from the 1H resonances is also studied.

Cross polarization, radio frequency field homogeneity, and circuit balancing in high field solid state NMR probes.

Homogeneous radio frequency (RF) fields are important for sensitivity and efficiency of magnetization transfer in solid state NMR experiments. If the fields are inhomogeneous the cross polarization (CP) experiment transfers magnetization in only a thin slice of sample rather than throughout the entire volume. Asymmetric patterns have been observed in plots of the CP signal versus RF field mismatch for an 800 MHz solid-state NMR probe where each channel is resonated in a single-ended mode.

The HBP1 transcriptional repressor and the p38 MAP kinase: unlikely partners in G1 regulation and tumor suppression.

Mechanisms that inhibit cell cycle progression and establish growth arrest are fundamental to tumor suppression and to normal cell differentiation. A complete understanding of these mechanisms should provide new diagnostic and therapeutic targets for future clinical applications related to cancer-specific pathways. This review will focus on the HMG-box protein 1 (HBP1) transcriptional repressor and its roles in cell cycle progression and tumor suppression.

Assignments of carbon NMR resonances for microcrystalline ubiquitin.

Solid-state NMR 2D spectroscopy was used to correlate carbon backbone and side-chain chemical shifts for uniformly (13)C,(15)N-enriched microcrystalline ubiquitin. High applied field strengths, 800 MHz for protons, moderate proton decoupling fields, 80-100 kHz, and high magic angle sample spinning frequencies, 20 kHz, were used to narrow the most of the carbon line widths to 0.5-0.

Linear phase correction of folded multidimensional NMR data by zero inter-filling.

We describe a procedure to enable linear phase correction of extensively folded multidimensional NMR data. This involves adding zeros in between data points in the indirect dimension to increase the effective bandwidth in the associated spectral window. A standard linear phase correction can then be applied to the data and a properly phased spectrum obtained after additional shuffling of the data in many instances.

Sensitive high resolution inverse detection NMR spectroscopy of proteins in the solid state.

A new indirect detection scheme for obtaining (15)N/(1)H shift correlation spectra in crystalline proteins is described. Excellent water suppression is achieved without the need for pulsed field gradients, and using only a 2-step phase cycle. Careful attention to overall NMR instrument stability was found critical for obtaining the best resolution and sensitivity.

High-sensitivity observation of dipolar exchange and NOEs between exchangeable protons in proteins by 3D solid-state NMR spectroscopy.

A highly sensitive new 1H-detected 3D solid-state NMR method is described for characterizing 1H-1H spin exchange in nanocrystalline samples of 15N- and 2H-enriched protein. Long-range contacts are observed in human ubiquitin. The method is also used to show that numerous NOEs between backbone amides and crystal water protons can be observed.

The influence of internuclear spatial distribution and instrument noise on the precision of distances determined by solid state NMR of isotopically enriched proteins.

The relative merits of different isotopic enrichment strategies that might be used in solid state NMR protein structure determinations are explored. The basis for comparison of these merits is the determination of the relative uncertainties in rates measured by a generalized dipolar recoupling experiment. The different schemes considered use (13)C, (15)N and (2)H labeling of ubiquitin with homonuclear magnetization-transfer type experiments under magic-angle spinning (MAS).