Novel intramolecular reductive C-C coupling during borohydride reduction of a bi-enone

Borohydride reduction of the bi-enone (1) gave the structurally and mechanistically interesting compounds (4) and (5a-c) resulting from intramolecular carbon-carbon coupling.

Structure of l-Diphenylmethyl-3-hydroxyazetidinium Chloride,* C 16 H lsN O+.CI -

M r=275.8, monoclinic, P21/a, a= 12.356 (5), b=9.054 (4), c= 14.043 (4) A, t= 100.34 (3) ° , V=1545.5A 3, Z=4, D,,,= 1.14, D x = 1.185 Mg m -3, p(Mo Ka, /l = 0.7107 ]k) = 2.77 mm -1, F(000) = 584.0, T= 293 K, R = 0.053 for 1088 reflections. The four-membered ring is buckled 13.0 ° (0= 167.0°). The azetidinium moiety is linked to the C1- ion through a hydrogen bond [O-H...C1 = 3.166 (5) A].

A hypothesis on the role of hydroxyproline in stabilizing collagen structure

The possibility of hydroxyproline residues stabilizing the collagen triple-helical structure by the formation of additional hydrogen bonds through their γ-hydroxyl group has been studied from structural considerations. It is not possible for this hydroxyl group to form a direct hydrogen bond with a suitable group in a neighbouring chain of the triple-helical protofibril. However, in the modified one-bonded structure, which is stabilized by additional hydrogen bonds being formed through water molecules as intermediaries (put forward in 1968 by Ramachandran, G. N. and Chandrasekharan, R.), it is found that the γ-hydroxyl group of hydroxyproline can form a good hydrogen bond with the water oxygen as acceptor, the hydrogen bond length being 2.82 Å. It is proposed that, in addition to stabilizing the collagen triple-helical structure due to the stereochemical properties of the pyrrolidine ring, hydroxyproline gives added stability by the formation of an extra hydrogen bond. Experimental studies on the determination of shrinkage and denaturation temperatures of native collagen and its synthetic analogues, as a function of their hydroxyproline content, are being undertaken to test this hypothesis.

Conformation And C-N Rotational Barrier Of Dithiocarbamate Esters Nmr And Molecular-Orbital Studies

The variable temperature proton and ambient temperature carbon-13 NMR spectra of S-methyl dithiocarbamate esters have been recorded. The results of the theoretical energy calculations (CNDO/2 and EHT types) together with the experimental data have been interpreted in terms of the molecular conformations. The barrier heights for the rotation about the thioamide C—N bond are calculated using the CNDO/2 method and the results are discussed in terms of the computed charge densities and bond orders.

Cross Talk between Receptor Guanylyl Cyclase C and c-src Tyrosine Kinase Regulates Colon Cancer Cell Cytostasis

Increased activation of c-src seen in colorectal cancer is an indicator of a poor clinical prognosis, suggesting that identification of downstream effectors of c-src may lead to new avenues of therapy. Guanylyl cyclase C (GC-C) is a receptor for the gastrointestinal hormones guanylin and uroguanylin and the bacterial heat-stable enterotoxin. Though activation of GC-C by its ligands elevates intracellular cyclic GMP (cGMP) levels and inhibits cell proliferation, its persistent expression in colorectal carcinomas and occult metastases makes it a marker for malignancy. We show here that GC-C is a substrate for inhibitory phosphorylation by c-src, resulting in reduced ligand-mediated cGMP production. Consequently, active c-src in colonic cells can overcome GC-C-mediated control of the cell cycle. Furthermore, docking of the c-src SH2 domain to phosphorylated GC-C results in colocalization and further activation of c-src. We therefore propose a novel feed-forward mechanism of activation of c-src that is induced by cross talk between a receptor GC and a tyrosine kinase. Our findings have important implications in understanding the molecular mechanisms involved in the progression and treatment of colorectal cancer.

Role of heme in the synthesis of cytochrome c oxidase in Neurospora crassa

The role of heme in the synthesis of cytochrome c oxidase has been investigated in the mold Neurospora crassa. Iron-deficient cultures of the mold have low levels of cytochrome oxidase and delta-aminolevulinate dehydratase, the latter being the rate-limiting enzyme of the heme-biosynthetic pathway in this organism. Addition of iron to the iron-deficient cultures results in an immediate increase in the levels of delta-aminolevulinate dehydratase followed by an increase in the rate of heme synthesis and cytochrome oxidase levels. The rate of precursor labeling of the mitochondrial subunits of cytochrome oxidase is decreased preferentially under conditions of iron deficiency and addition of iron corrects this picture. Exogenous hemin addition which prevents iron-mediated induction of delta-aminolevulinate dehydratase also inhibits the increase in the activity of cytochrome oxidase and the enhanced precursor labeling of the mitochondrial subunits of cytochrome oxidase. Protein synthesis on mitoribosomes measured in vivo and in vitro is decreased under conditions of heme deficiency. Hemin addition in vitro to mitochondrial lysates prepared from heme-deficient mycelia restores a near normal rate of protein synthesis. It is concluded that heme is required for the optimal rate of translation on mitoribosomes.

Construction of a cDNA clone for a nuclear-coded subunit of cytochrome c oxidase from rat liver

A cDNA library for 6S–9S poly(A)-containing RNA from rat liver was constructed in Image . Initial screening of the clones was carried out using single stranded 32P-labeled cDNA prepared against poly(A)-containing RNA isolated from immunoadsorbed polyribosomes enriched for the nuclear-coded subunit messenger RNAs of cytochrome c oxidase. One of the clones, pCO89, was found to hybridize with the messenger RNA for subunit VIC. The DNA sequence of the insert in pCO89 was carried out and it has got extensive homology with the C-terminal 33 amino acids of subunit VIC from beef heart cytochrome c oxidase. In addition, the insert contained 146 bp, corresponding to a portion of the 3′-non-coding region. Northern blot analysis of rat liver RNA with the nick-translated insert of pCO89 revealed that the messenger RNA for subunit VI would contain around 510 bases.

Purification, properties and induction of a specific benzoate-4-hydroxylase from Aspergillus niger (UBC 814)

An inducible benzoate-4-hydroxylase has been partially purified from crude extracts of the mycelial felts of Aspergillus niger. This enzyme catalyzes the transformation of benzoate to p-hydroxybenzoate with equimolar consumption of NADPH and O2. It requires tetrahydropteridine as a prosthetic group. The optimum activity was found at pH 6.2 with a Km value at 30°C of 1.6 · 10−4 M for NADPH and 1.3 · 10−4 M for benzoate. Fe2+ (iron) is required for the enzyme activity. The enzyme is stabilized by the inclusion of benzoate, EDTA and glutathione in the extracting buffer. The enzyme is specific for benzoate as substrate. Sulfhydryl group(s) are essential for enzyme activity as indicated by p-chloromercuri-benzoate and N-ethylmaleimide inactivation. Benzoate-4-hydroxylase activity is decreased in the mycelial felts of Aspergillus niger grown in the presence of higher concentrations of benzoate. Maximum activity of the enzyme was observed at 36 h after inoculation.

Moiré Displacement Transducer for N/C Systems

Noncontact method of sensing accurately the magnitude and direction of displacements is essential in systems such as the numerically controlled machines. A displacement transducer, using Moiré transmission gratings is described. The notable feature of this instrument is that it requires only gratings of small lengths, even for measurement of large displacements.

D.c. and a.c. polarographic behaviour of vanadium-glycine complexes

A detailed investigation of the d.c. polarographic behaviour of vanadium(V),-(IV) and -(III) in glycine solutions has been made keeping the total glycine concentration at 0.1, 0.5 and 1.0 M and varying the pH of the solution. Experiments keeping the pH constant (using different ratios of glycine and glycine anion) and varying the glycine anion concentration, and also in predominantly anion solutions, have been made.

Load-Deflection Behavior of Restrained R/C Skew Slabs

A method is presented for determining the complete load-deflection behavior of reinforced concrete skew slabs restrained at the edges and subjected to uniformly-distributed loading. The analysis is considered in three stages. In the first stage the load-deflection behavior up to the cracking load is considered. The behavior between the cracking load and the yield line load is considered in the second stage. The load-deflection behavior beyond the yield line load, taking into account the effect of the membrane action, is considered in the third stage. Details of an experimental program of casting and testing 12 reinforced concrete skew slabs restrained at the edges are presented to verify the results of the analysis.

Finite element analysis of rotors

A finite element formulation for the natural vibration analysis of tapered and pretwisted rotors has been presented. Numerical results for natural frequencies for various values of the geometric parameters and rotational speeds, have been computed for the case of rotors with and without pretwist. A Galerkin solution for the fundamental has also been worked out and has been used to provide a comparison for the finite element results. Charts for rapid estimation of the fundamental frequency parameter of tapered rotors, have been included.