The association between KL polymorphism and prostate cancer risk in Korean patients.

The Klotho (KL) gene is a classical "aging suppressor" gene. Although recent studies have shown that KL participates in the progression of several types of human cancers, the relationship between KL polymorphism and prostate cancer was unknown. The present study aimed to investigate the association between KL genetic polymorphisms and prostate cancer. Twenty-five common single nucleotide polymorphisms (SNPs) in KL gene (including KL gene polymorphism C1818T in exon 4) were assessed in 272 prostate cancer cases and 173 controls. Single-locus analyses were conducted using unconditional logistic regression. In addition, we did a haplotype analysis for the 25 KL SNPs tested. CC genotype of C1548T KL polymorphism had approximately twofold increased prostate cancer risk compared with the homozygous genotype TT and heterozygote CT (odds ratio 1.85 [95% CI, 1.09-3.12], P = 0.02). We also found that non-T allele carriers had significantly higher prostate cancer risk associated with the prostate cancer clinical characteristics (tumor stage or Gleason score). Our findings suggested that the C1548T polymorphism of KL gene is associated with the prostate cancer and may act as a risk factor for the development of prostate cancer.

Cu(II) cyclen cleavage agent for human islet amyloid peptide.

Type 2 diabetes mellitus (T2DM) is characterized by a substantial reduction in beta-cell mass and the amyloid fibrils which are formed by the aggregation of the human islet amyloid polypeptide (h-IAPP) in the islet of Langerhans. Cleavage agents with Co(III) cyclen as the catalytic group have been studied as a novel therapeutic option for T2DM patients. However, recent research has suggested that the cytotoxicity of h-IAPP might be mediated by interactions with Cu(II); furthermore, it has been shown in vitro that Cu(II) prevents h-IAPP from forming the beta-sheet conformers. Therefore, we synthesized a cleavage agent using Cu(II) cyclen. The resulting cleaved fragments and estimated cleavage yield (8.3mol%) were evaluated after incubation with h-IAPP.

Origins of isotopomeric polymorphism.

The complex formed between 4-methylpyridine and pentachlorophenol (4MPPCP) crystallises in a triclinic space group. If the same complex is synthesized from deuterated pentachlorophenol, it crystallizes in an entirely different monoclinic polymorph. Using solid-state NMR of samples synthesized with a full range of deuteration levels, crystallized from solution or the melt, and in the presence or absence of seeds, we have confirmed that the isotopomers indeed have different thermodynamically stable crystal structures. The roots of this phenomenon of isotopomeric polymorphism apparently lie in the differences in hydrogen bonding between the polymorphs. The triclinic form has a relatively short hydrogen bond. High-field solid-state NMR shows both the 1H chemical shift and the 2H electric quadrupole coupling of the hydrogen involved in the bond to be strongly temperature-dependent, indicating a low-lying excited state of the hydrogen bond longitudinal vibration. Inelastic neutron scattering of isotopomers of 4MPPCP has allowed us to identify the three orthogonal vibrational modes of the hydrogen in the hydrogen bond, at 29.7, 145, and 205 meV (240, 1168, and 1651 cm(-1)). The longitudinal mode is the lowest in energy, and it indicates a slightly asymmetric low-barrier double-well potential. Intrinsic to such potentials is a very small difference in zero-point energies (ZPEs) between the protonated and deuterated forms. As a contrast, the monoclinic form has a comparatively normal hydrogen bond, in which the proton and deuteron ZPEs should be different by approximately 500 cm(-1). A scenario can be envisaged where the triclinic protonated form is lower in energy than the monoclinic protonated form, but the triclinic deuterated form is higher in energy than the monoclinic deuterated form. This evidently accounts for the difference in relative stabilities of the two forms upon isotope substitution.

Orientation of single crystals using linear approximations to NMR transits.

We have derived analytical expressions for determining the orientation of high-symmetry single crystals from line-crossings in a single rotation plot. We demonstrate the utility of the method using the strontium-87 resonance in strontium nitrate. Employing our new method, which we call orientation of single crystals using linear approximations to NMR transits (OSCULANT), in combination with fourth-order perturbation theory, we obtain a highly accurate value for the quadrupole coupling constant, and an estimate for the chemical shielding anisotropy.

Development and evaluation of N-hydroxysuccinimide-activated silica for immobilizing human serum albumin in liquid chromatography columns.

A method was developed for preparing N-hydroxysuccinimide (NHS)-activated silica for use in immobilizing human serum albumin (HSA) within HPLC columns. This support was made by reacting aminopropyl silica with disuccinimidyl suberate (DSS). Solid state 13C NMR was used to examine the steps in this synthesis. The number of NHS groups on the silica's surface was controlled by varying the amount of DSS or density of surface amine groups used in the preparing this material. Items considered in the use of this material for the immobilization of HSA included the amount of protein added to the support, the reaction time, and the pH of the coupling buffer. These supports were then evaluated in terms of their ability to perform chiral separations for R/S-warfarin and D/L-tryptophan. Advantages of this method compared to current immobilization techniques for HSA included its better long-term stability and the fact that it did not require the use of any reducing agents. The approaches developed in this work are not limited to HSA but can be used with other proteins or amine-containing ligands.

Isotopomeric polymorphism.

The complex formed between 4-methylpyridine and pentachlorophenol (4MPPCP) crystallizes in a triclinic space group. If the same complex is synthesized from deuterated pentachlorophenol (4MPPCP-d1), it crystallizes in an entirely different monoclinic polymorph. Solid-state NMR of samples synthesized with a full range of deuteration levels, crystallized from solution or the melt, and in the presence or absence of seeds confirms that the isotopomers indeed have different thermodynamically stable crystal structures. The phenomenon is apparently due to very different hydrogen bond strengths between the two polymorphs.

207Pb NMR of Solid Solutions of Divalent Metal Nitrates.

207Pb NMR spectra of mixed crystals of anhydrous lead and strontium nitrate show up to 13 lines, arising from lead ions with 0-12 Pb(2+) nearest-neighbor cations replaced by Sr(2+). The shifted lines are further split by the multiplicity of inequivalent nearest-neighbor replacements. The average shift per Sr(2+) ion is 21.8 ppm. Similar but somewhat smaller effects are seen in [Pb,Ba](NO(3))(2) mixed crystals. The intensities of the resonances can be fit to Monte Carlo models of Pb(2+) and Sr(2+) ion distributions and are consistent with like nearest-neighbor pairs being 120 J/mol lower in energy than unlike pairs.