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Biomedical subjects

I C Smith

Publications and source records attributed to I C Smith.

At least 199 records · Page 11Linked to original sources
PubMed1978

Assignment by 13-C-NMR spectroscopy of configuration at C-5 in 17 alpha-ethylestran-17 beta-ol, an impurity in the anabolic steroid ethylestrenol.

The stereochemistry at C-5 in 17 alpha-ethylestran-17 beta-ol, found as an impurity in ethylesterenol, was assigned by 13C-NMR spectroscopy. The hydrogen atom attached to C-5 is in the alpha-configuration. Resonance assignments were confirmed by partial deuteration, off-resonance 13C-(1H)-decoupling, and comparison with model compounds.

Carbon Isotopes↗
PubMed1978

Sterol ordering effects and permeability regulation in phosphatidylcholine bilayers. A comparison of ESR spin-probe data from oriented multilamellae and dispersions.

The effects of a series of sterols on molecular order and motion in bilayers formed from egg lecithin and dicetylphosphate were examined and correlations between order and data on permeability to 22Na+ were sought. Electron spin resonance spectra were observed for probes intercalated both in multilamellar dispersions where the effects of motion and orientation are difficult to separate, and in planar multibilayers where the degree of molecular order may be measured even in the presence of slow probe motion. It was concluded from the planar multi-bilayer data that sterols which increase the degree of ordering of lipid molecules decrease 22Na+ permeability, and that sterols which have the opposite effect on order increase permeability. All the sterols tested lead to decreased rates of motion of the probes. This effect obscures the correlation between order and permeability using data from dispersions.

Chemical Phenomena↗
PubMed1977

The influence of glycyl residues on the flexibility of peptide hormones in solution. A 13C-nuclear-magnetic-resonance study of luteinizing hormone-releasing hormone (luliberin) and its des-glycinamide10 N-ethylamide analog.

13C nuclear magnetic resonance spectroscopy in used to gain information on the flexibility of the backbone in peptide hormones and peptide hormone analogs. 13C spin-lattice relaxation times (T1) were measured on luliberin, the luteinizing-hormone-releasing hormone and des(Gly-NH2)10-luliberin-N-ethylamide in aqueous solution at 25.2 and 67.9 MHz at temperatures of 32 degrees, 40 degrees and 55 degrees C. The 13C spin-lattice relaxation times indicate increased flexibility of the peptide backbone in the immediate environment of glycyl residues in luliberin (less than Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) and the hormone analog des(Gly-NH2)10-luliberin-N-ethylamide (less than Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-NH-CH2CH3) in aqueous solutions. 13 C NMR spectroscopy is shown to be a sensitive technique for monitoring the time-averaged conformational flexibility of peptides in solution. Activation energies (Ea) of about 25 kJ/mol were obtained for rotational reorientation of non-terminal alpha-carbons in the peptide backbone. Rotation of methyl groups was characterized by an Ea of 9.6 kJ/mol whereas reorientation of the N-terminal pyroglutamyl residue showed an Ea value of 14.6 kJ/mol. The Ea values of individual carbons in the side-chains of prolyl, arginyl and leucyl residues in the peptides were similar to those obtained for the alpha-carbon of the same amino acid residue in the peptide backbone of the hormones.

Calorimetry↗
PubMed1977

Quantitative analysis of degradation products in pilocarpine hydrochloride ophthalmic formulations.

The presence of isopilocarpine, an epimer of pilocarpine, and of pilocarpinic acid, a hydrolytic degradation product of pilocarpine, was established and all three substances were assayed in various commercial ophthalmic formulations of pilocarpine hydrochloride by 13C-Fourier transform spectroscopy. Assay was based upon integrated intensities of selected resonances from any formulation calibrated against the intensity of tetramethylammonium bromide, used as a common external reference. The normalized intensities were then related to those of a reference solution of pilocarpine hydrochloride, thereby eliminating any factor arising from variability of 13C-relaxation times. The 13C-resonance for the N-methyl group, being common to all products, provides a convenient basis for the assay of the total alkaloid content whereas the C-8 resonances are best suited for assaying residual pilocarpine and its degradation products. This procedure, estimated as accurate to +/- 5%, constitutes the first comprehensive analytical method to differentiate between pilocarpine and its degradation products.

Carbon Isotopes↗
PubMed1977

Strucutres of the capsular polysaccharides of Neisseria meningitidis as determined by 13C-nuclear magnetic resonance spectroscopy.

The application of 13C-nuclear magnetic resonance spectroscopy to the structural determination of the capsular polysaccharide antigens of Neisseria meningitidis is described. Complete assignments of the spectra of the polysaccharides of serogroups A, B, C, W-135, X and Y were made and were based mainly on previous assignments made for the monomer units of the respective polysaccharides. This technique provides information on all structural aspects of the polysaccharides including composition, mode of linkage, location of O-acetyl substituents, sequence, and conformation. In addition, nuclear magnetic resonance is nondestructive, extremely rapid, and has enormous potential in bacteriological research.

Acetylation↗
PubMed1976

A carbon-13 nuclear magnetic resonance study of hyperactive and hypoactive derivatives of luteinizing hormone-releasing hormone: des-Gly-NH210-[DLeu6]LH-RH ethylamide and des-Gly-NH210-[L-Leu6]LH-RH ethylamide.

The carbon-13 (13C) nuclear magnetic resonance (NMR) behavior of the hyperactive analogue of luteinizing-hormone-releasing hormone (LH-RH), des-Gly-NH2(10)-[D-Leu6]LH-RH ethylamide, has been studied. The spectra are compared with those of the hypoactive des-Gly-NH2(10)-[L-Leu6]LH-RH ethylamide. Spin-lattice relaxation times (T1) of 13C at natural abundance have been obtained for both peptides at 25 and 68 MHz in aqueous solution and used as monitors of flexibility at each carbon atom in the peptide backbone and side chains. The [D-Leu6]-and [L-Leu6]-sub-stituted analogues show equal degrees of freedom within the peptide backbone and side chains. Substitution of the glycine amide moiety in position 10 by an ethylamide group causes an increase in flexibility of the backbone at that position. The increase in flexibility is not transmitted to the adjacent prolyl residue. The C-terminal peptide link at position 10 is proposed to restrict the flexibility of the prolyl residue in position 9, thus maintaining the motional characteristics of the LH-RH peptide backbone in the des-Gly-NH2(10)-[Leu6]LH-RH ethylamide analogues. There were no significant differences in the 13C chemical shifts or T1 values between the hypoactive and hyperactive analogues in aqueous solution which would explain the differences in biological activity. Interaction between receptor and hormone may thus be required to induce, or select, the biologically active conformation of the hormone.

Amides↗
PubMed1976

Molecular motion and order in single-bilayer vesicles and multilamellar dispersions of egg lecithin and lecithin-cholesterol mixtures. A deuterium nuclear magnetic resonance study of specifically labeled lipids.

Deuterium (2H) nuclear magnetic resonance (NMR) quadrupole splittings and relaxation times have been measured for a variety of specifically deuterated lipids intercalated in lamellar-multibilayer dispersions and single-bilayer vesicles of egg lecithin and lecithin-cholesterol mixtures. The deduced order parameters and relaxation times vary with position of deuteration, acyl chain length, unsaturation, and temperature. The order parameters and spinlattice relaxation times T1 indicate rapid intramolecular motions of restricted amplitude in both the choline head group and hydrocarbon chains. The ordering profile for the acyl chains is similar to that predicted by statistical-mechanical theory. The order parameters yield estimates of the bilayer thickness and linear coefficient of expansion in close agreement with the x-ray determinations. A comparison of the deuterium and electron spin resonance spinprobe order parameters demonstrates the perturbation of the bilayer by the bulky nitroxide probe. The transverse relaxation time T2 for single-bilayer vesicles is quantitatively accounted for by a simple modification of classical relaxation theory which takes into account the modulation of the static quadrupole interaction by rapid local molecular motions and the modulation of the residual quadrupole interaction by the slower overall tumbling of the vesicle. It is unambiguously demonstrated that molecular motion and order in single-bilayer vesicles are very similar to those in lamellar multibilayers. Significant differences occur only for a few segments near the terminal methyl groups of the acyl chains, where the order parameters for vesicles are 10-30% smaller than those found for lamellae. The incorporation of cholesterol in lecithin bilayers is shown to increase the degree of orientational order in vesicles and lamellae, and to increase the hydrodynamic radius of vesicles. Thus, single-bilayer vesicles and multilamellar dispersions of phospholipids are equally useful models for biological membranes. They yield equivalent information about the internal organization and mobility of lipid bilayers, when the spectral manifestations of overall vesicle motion are correctly taken into account.

Binding Sites↗
PubMed1976

A deuterium nuclear magnetic resonance study of the condensing effect of cholesterol on egg phosphatidylcholine bilayer membranes. I. Perdeuterated fatty acid probes.

Deuterium nuclear magnetic resonance quadrupole splittings Dq and the related acyl chain segmental order parameters Smol have been determined for perdeuteriostearic acid intercalated as a molecular probe in the lamellar liquid crystalline phase of egg yolk phosphatidylcholine-cholesterol-water mixtures. The 2H NMR data show that cholesterol induces a high degree of order in the acyl chains of the phospholipid while maintaining the general profile of high order near the head group and relatively low order in the middle of the bilayer. This results in a pronounced thickening of the bilayer and concomitant decrease in the average molecular area of the fatty acyl chains. The giometrical changes in the bilayer due to cholesterol are discussed in terms of trans-gauche isomerization in the fatty acyl chains. The picture of the condensing effect revealed by 2H NMR is consistent with that from previous X-ray diffraction experiments. No evidence for a specific complex between cholesterol and phosphatidylcholine is apparent. The condensing effect of cholesterol is attributed to interaction between the fatty acyl chains and the rigid steroid nucleus, and to solvation of the 3beta-hydroxyl group at the aqueous interface.

Binding Sites↗
PubMed1976

A conformational study of adenylyl-(3',5')-adenosine and adenylyl-(2',5')-adenosine in aqueous solution by carbon-13 magnetic resonance spectroscopy.

The solution conformation of adenylyl-(3',5')-adenosine and adenylyl-(2',5')-adenosine in both the stacked and unstacked states was studied by carbon-13 magnetic resonance spectroscopy. Large chemical shift differences between the base carbons in the dimers and those in the corresponding monomers are attributed in part to the influence of base-base interaction. Carbon-phosphorus couplings across three bonds revealed the preferred populations for certain backbone rotamers, demonstrating that significant changes in conformation about the "c(3')-O and C(5')-O bonds do not occur in the temperature or salt-induced unstacking of adenylyl-(3',5')-adenosine. However, rotations about the C(2')-O and C(5')-O bonds occur in the temperature-mediated unstacking of adenylyl-(2',5')-adenosine.

Adenosine↗
PubMed1976

Structural determination of the polysaccharide antigens of Neisseria meningitidis serogroups Y, W-135, and BO1.

The purified high molecular weight serogroup Y meningococcal polysaccharide contains equimolar proportions of D-glucose and N-acetylneuraminic acid and is partially O-acetylated. Carbon-13 nuclear magnetic resonance (NMR) studies, together with other chemical data, have indicated that the polysaccharide is linked only at C-6 of the D-glucose and C-4 of the sialic acid residues, all the linkages being in the alpha-configuration. The 13CNMR data also indicated that the Y polysaccharide is composed of an alternating sequence of these two different residues, and this was confirmed by its autohydrolysis where the major product was 4-O-alpha-D-glucopyranosyl-beta-D-N-acetylneuraminic acid. The W-135 polysaccharide differs from that of Y only in the absence of O-acetylation and in the configuration of one hydroxyl group of the disaccharide repeating unit. In this case autohydrolysis yielded 4-O-alpha-D-galactopyranosyl-beta-D-N-acetylneuraminic acid as the major product. Structural evidence indicates that the BO and Y polysaccharides are identical. Methanolysis of the Y polysaccharide yielded in addition to the methyl glycosides of glucose and sialic acid, a 9-O-acetyl derivative of the latter. This derivative was formed during the re-N-acetylation process and its formation was mainly due to the presence of sodium ions in the original polysaccharide.

Antigens, Bacterial↗