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At least 217 records · Page 12Linked to original sources
PubMed1993

Comparative conformational analysis and in vitro pharmacological evaluation of three cyclic hexapeptide NK-2 antagonists.

The conformational analysis of three cyclic hexapeptides is presented. Cyclo-(-Gln6-Trp7-Phe8-Gly9-Leu10-D-Met11-) (1) and cyclo-(-Gln6-Trp7-Phe8-Gly9-Leu10-Met11-) (2) are NK-2 antagonists in the hamster trachea assay, whereas cyclo-(-Gln6-Trp7-Phe8-(R)-Gly9-[ANC-2]Leu10-Met11+ ++-) (3), where Gly9[ANC-2]Leu10 represents (2S)-2-((3R)-3-amino-2-oxo-1-pyrrolidinyl)-4-methylpentanoyl, is inactive as agonist and antagonist in this assay. In DMSO, the NMR results cannot be interpreted as being consistent with a single conformation. However, the combined interpretation of results from NMR spectroscopy, restrained molecular dynamics simulations with application of proton-proton distance information from ROESY spectra, and pharmacological results leads to a reduced number of conformational domains for each peptide, which can be compared with each other and may be classified as responsible for their biological activity. Trying to match the conformational domains approximately with regular beta- and gamma-turns, we find a gamma n-turn at the position of the methionine occurring in all peptides. For the active peptides 1 and 2 we arrive at an inverse gamma i-turn at Phe8, and beta I'- or beta II-turns with Gly9 and Leu10 at the corner positions, these beta-turns having a similar topology with respect to the linking peptide unit. Other conformational domains common to only 1 and 2 support their classification as responsible for the biological activity.

Amino Acid Sequence↗
PubMed1994

The cyclic structure of the enterococcal peptide antibiotic AS-48.

The complete primary structure of the peptide antibiotic AS-48 produced by Enterococcus faecalis has been determined by chemical degradation analysis. The cyclic nature of this 70 residues containing peptide was demonstrated by plasma desorption mass analysis of the generated peptides and electrospray ionisation mass analysis of the native polypeptide. As far as we know, this is the first example of an antibiotic protein cyclised by a tail-head peptide bond formation and not by branching of the polypeptide side chains.

Amino Acid Sequence↗
PubMed1983

Cyclodextrin glycosyltransferases from Klebsiella pneumoniae M 5 al and Bacillus macerans: quantitative analysis by high-performance liquid chromatography of the (1 leads to 4)-alpha-D-glucopyranosyl transfer-products from some linear and cyclic substrates.

The analysis of the (1 leads to 4)-alpha-D-glucopyranosyl transfer-products from some linear and cyclic substrates by quantitative h.p.l.c. illuminated the mode of action of the cyclodextrin glycosyltransferases [1 leads to 4)-alpha-D-glucan:[(1 leads to 4)-alpha-D-glucopyranosyl]transferase (cyclising), EC 2.4.1.19) from Klebsiella pneumoniae M 5 al and Bacillus macerans. D-Glucopyranosyl transfer, obligatory for maltose (poor substrate), was preferred for maltotriose (good substrate). The lengths of linear disproportionation-products increased with the lengths of the linear substrates. Cyclodextrins were produced from maltotriose and maltopentaose, but not from maltose. The cyclodextrins were substrates in the absence of acceptors. The cyclodextrin transformation started without the formation of detectable amounts of linear transfer-products. The cyclodextrin composition of long-term digests was nearly the same with all the cyclic substrates, cycloheptaamylose being the main cyclic compound. The linear carbohydrate was uniformly distributed from maltose up to at least maltononaose. The enzyme from Bacillus macerans was the least active, but long-term digests yielded results comparable to those obtained with the enzyme from Klebsiella pneumoniae M 5 al.

Bacillus↗
PubMed1982

Unusual intramolecular hydrogen bonding in cycloamanide A, cyclic (LPro-LVal-LPhe-LPhe-LAla-Gly). A crystal structure analysis.

The naturally occurring cyclic hexapeptide, cycloamanide A, has only one intramolecular hydrogen bond. It is a 4 leads to 1 type that encompasses the L Phe-L Ala sequence in which the experimentally determined phi, psi values are +54 degrees, -118 degrees and -88 degrees, -4 degrees, respectively. Even though the chirality is L, L, the phi, psi values are characteristic for a D, L beta-bend, Type II'. The conformation of the molecule was established by a crystal structure determination using X-ray diffraction analysis. Cycloamanide A (C33H42N6O6 . 4H2O) crystallizes in space group P2(1)2(1)2(1) with cell parameters a = 13.307(2) A, b = 24.820(4)A and c = 11.231(1)A.

Hydrogen Bonding↗
PubMed1967

Synthesis of fatty aldehydes and their cyclic acetals (new derivatives for the analysis of plasmalogens).

Saturated and unsaturated fatty aldehydes were prepared in good yield by the reduction of acid chlorides with lithium aluminum tri-t-butoxy hydride. Saturated odd and even numbered aldehydes were prepared by the ozonolysis-reduction of 1-alkenes. Ozonides were hydrogenated with a Lindlar catalyst or reduced with dimethyl sulfide. Several diols, including 1,3-propanediol and ethylene glycol, were used to synthesize cyclic acetals from aldehydes and plasmalogens in quantitative yield. Cyclic acetals were synthesized from 2,4-dinitrophenyl hydrazones when an exchanger such as acetone or acetylacetone was included in the reaction mixture. A number of physical and chemical properties indicate that cyclic acetals are stable compounds which do not decompose during storage or gas-liquid chromatographic (GLC) analysis. The cyclic acetals have unusually long retention volumes which are probably related to the large dipole moments found with cyclic compounds. These derivatives are, therefore, readily separated from their aldehyde and methyl ester analogues on polar and nonpolar stationary phases. GLC analysis of the aldehydogenic moieties in plasmologens may be conveniently carried out by direct conversion to cyclic acetals without preliminary isolation of aldehydes or removal of methyl esters by saponification.

Aldehydes↗
PubMed1983

[Usefulness of the determination of nephrogenous cyclic AMP in the diagnosis of primary hyperparathyroidism].

The analysis of nephrogenous cyclic AMP (NcAMP) has been reported to be a means of estimating parathyroid function with the advantage of being rapidly and easily performed. More specific than the analysis of urinary cyclic AMP (UcAMP), it measures biological activity of the parathyroid hormone. This study tests its use in the diagnosis of primary hyperparathyroidism (HPP) and compares the results of UcAMP with those of NcAMP. Analyses of NcAMP and parathyroid hormone were performed in a group of 21 healthy controls and two groups of hypercalcemic patients, one consisting of 12 patients with HPP and the other of 14 patients with hypercalcemia of non-parathyroid origin (HCa). It was confirmed that NcAMP is a parameter of parathyroid function, analysis of which allows the diagnosis of HPP with the same precision as analysis of the carboxyterminal plasma PTH. It has the added advantage over PTH measurements of detecting low values, thus permitting documentation of parathyroid inhibition in HCa patients.

Adolescent↗
PubMed1979

Cyclic nucleotide binding properties and molecular forms of the cyclic-AMP-dependent protein kinase from bovine eye lens.

The activity of the cyclic-AMP-dependent protein kinase found in the crude extract of bovine eye lens cortical fibers was increased by 10(-6) M cyclic AMP or 10(-5) M cyclic GMP to the same extent, However, the interaction between cyclic AMP and cyclic GMP in the course of binding to the cyclic-AMP-dependent protein kinase did not seem to be competitive. Scatchard analysis of cyclic GMP binding by the crude extract indicated the presence of two type of cyclic GMP binding sites (Kd1 about 2 . (10(-7) M, Kd2 about 5 . 10(-6) M). Different species of cyclic nucleotide binding fractions were separated by Sephadex G-200 gel chromatography of the crude extract. The bulk of the low affinity cyclic GMP binding activity was found in the exclusion volume. The cyclic-AMP-dependent protein kinase eluted in two fraction (apparent molecular weight 300 000 and 150 000) and both protein kinase fractions were accompanied by the high affinity cyclic GMP binding activity. However, the ratios of this activity to the cyclic AMP binding activity were different in the two fraction, suggesting that different molecular weight forms of the holoenzyme had different cyclic nucleotide binding properties.

Animals↗
PubMed1993

Changes in oestrogen receptor protein, mRNA expression and localization in the endometrium of cyclic and pregnant gilts.

Conceptus secretion of oestrogen on Day 11 of gestation is involved with establishment of pregnancy in the pig. Changes in oestrogen receptor (ER) protein, mRNA and cellular localization in the endometrium were evaluated during the oestrous cycle and early pregnancy of the gilt. In nonpregnant gilts, concentration of nuclear ER in the endometrium increased from Days 0 to 12 followed by a decline on Day 15 of the oestrous cycle. In pregnant gilts, changes in endometrial nuclear ER during Days 10, 12, 15 and 18 were similar to that in cyclic pigs. Analysis of endometrial ER mRNA expression did not detect any difference between cyclic and pregnant pigs between Days 10 and 15 postoestrus. Expression of ER mRNA in endometrium of cyclic and pregnant gilts was greatest on Day 10 followed by a decline on Day 15. Endometrial ER mRNA increased on Day 18 of the oestrous cycle, but remained low during pregnancy. Immunocytochemical localization of ER in the endometria of cyclic and pregnant gilts indicated that there was intense staining for ER in stromal cells and moderate to strong staining in surface and glandular epithelial cells during oestrus (Day 0) and Day 18 of the oestrous cycle. However, stromal ER staining was absent from Days 5 to 15 of the oestrous cycle and continued to be suppressed on Day 18 of pregnancy. Immunocytochemical staining of ER in the surface and glandular epithelium was readily detectable from Days 0 to 12 of the oestrous cycle and during pregnancy. Intensity of staining for ER declined in surface epithelial cells on Day 15 in both cyclic and pregnant pigs whereas positive staining for ER in glandular epithelium was absent. Staining for ER on uterine surface epithelial cells increased during pro-estrus (Day 18) of cyclic gilts but remained similar to Day 15 in pregnant gilts. Changes in endometrial ER protein, mRNA and localization in surface epithelium are consistent with a physiological role for conceptus oestrogen secretion in uterine function and maternal recognition of pregnancy in the pig.

Animals↗
PubMed1983

Adenosine 3',5'-cyclic monophosphate-dependent release of prolactin from GH3 pituitary tumour cells. A quantitative analysis.

The involvement of cyclic AMP in mediating regulatory peptide-controlled prolactin release from GH3 pituitary tumour cells was investigated. Cholera toxin and forskolin elicited concentration-dependent increases in both GH3 cell cyclic AMP content and prolactin release. The maximum rise in prolactin release with these agents was 2-fold over basal. 8-Bromo-cyclic AMP produced a similar stimulation of prolactin release. The phosphodiesterase inhibitor isobutylmethylxanthine also produced an increase in prolactin release and GH3 cell cyclic AMP content. However, the magnitude of the stimulated prolactin release exceeded that obtained with any other agent. Thyrotropin-releasing hormone (thyroliberin) and vasoactive intestinal polypeptide produced a concentration-dependent rise in both cell cyclic AMP content and prolactin release. However, only vasoactive intestinal polypeptide elicited an increase in cell cyclic AMP content at concentrations relevant to the stimulation of prolactin release. Vasoactive intestinal polypeptide and thyrotropin-releasing hormone, when used in combination, were additive with respect to prolactin release. Vasoactive intestinal polypeptide and forskolin, at concentrations that were maximal upon prolactin release, were, when used in combination, synergistic upon GH3 cell cyclic AMP content but were not additive upon prolactin release. In conclusion the evidence supports a role for cyclic AMP in the mediation of vasoactive intestinal polypeptide- but not thyrotropin-releasing hormone-stimulated prolactin release from GH3 cells. A quantitative analysis indicates that a 50-100% rise in cyclic AMP suffices to stimulate cyclic AMP-dependent prolactin release fully.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Gene expression profiling of acute spinal cord injury reveals spreading inflammatory signals and neuron loss.

We have completed the first large-scale gene expression study of acute spinal cord injury (SCI) in rat. Oligonucleotide microarrays containing 1,200 gene-specific probes were used to quantify mRNA levels, relative to uninjured controls, in spinal cords injured using a standard contusion model. Our results revealed a marked loss of neuron-specific mRNAs at the injury site. The surviving cells showed a characteristic inflammatory response that started at the injury site and spread to the distal cord. Changes in several mRNA levels were associated with putative regenerative responses in the spinal cord. Notably, phosphodiesterase 4, nestin, glia-derived neurite promoting factor, and GAP-43 mRNAs increased significantly. Other mRNAs clustered temporally and spatially with these regeneration-associated genes. Thus we have described global patterns of gene expression following acute SCI, and we have identified targets for future study and possible therapeutic intervention.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Asymmetrical trajectory formation in cyclic forearm movements in man.

Predictions of the minimum-jerk model for a human cyclic motion were given in terms of asymmetry in movement trajectories. A detailed kinematic analysis of cyclic forearm motion, i.e., extension/flexion movements around the elbow joint in a horizontal plane ranging in frequency from 2-5.5 Hz, was made to examine the validity of the predictions. The kinematics of the trajectories were described in terms of deviation from symmetry in velocity and acceleration profiles, and jerk cost. The asymmetry could be accounted for by the solution of the minimum-jerk model using the boundary condition differences between extension and flexion during a movement cycle. The trajectory was asymmetrical at relatively low frequencies, and symmetrical at higher frequencies; the frequency boundary from asymmetrical to symmetrical trajectories differed among subjects with a range of 3-4.3 Hz. It was suggested for the asymmetrical trajectory formation that consecutive extension and flexion in a cycle could be processed as a unit in which speed and acceleration in each direction were differentiated. The shift from asymmetrical to symmetrical trajectories with increasing frequency was accompanied by a reduction in jerk cost and mechanical energy. The oscillators underpinning the high frequency movements were mainly non-linear. The results suggested a shift of control from the "rhythmic" sequencing of extension and flexion which resulted in trajectory asymmetry, to non-linear oscillation with no directional difference.

Adult↗
PubMed1975

Correlation between adenosine 3',5'-cyclic monosphosphate levels, adenylate cyclase activity, and adenosine 3',5'-cyclic monophosphate phosphodiesterase activity in tissue culture cells stimulated by serum.

Changes in the activity of adenylate cyclase [EC 4.6.1.1] of serum-stimulated hamster BHK cells in culture were investigated in relation to changes in the intracellular level of adenosine 3',5'-cyclic monophosphate (cyclic AMP). Addition of calf serum to quiescent cultures decreases the activity of adenylate cyclase, followed by cellular DNA synthesis. Cyclic AMP levels drop in parallel with the decrease in adenylate cyclase activity. Kinetic analysis of cyclic AMP phosphodiesterase [EC 3.1.4.17] revealed that BHK cells contain two forms of the enzyme, one with a Km of 0.77 muM and the other with Km of 17.0 muM. The activity of these enzymes is not affected by the addition of serum to tissue culture cells. The findings indicate that the decrease in adenylate cyclase activity is directly responsible for the decrease in cyclic AMP levels that is observed immediately after serum addition. Low levels of cyclic AMP continue for several hours during serum treatment, followed by a transient increase in cyclic AMP in the early stages of cellular DNA synthesis, at which time the activity of cyclic AMP phosphodiesterase with a low Km shows a slight decrease.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1988

[Post-transitional cycles and prey-predator models].

"This paper investigates the logical consistency of the mathematical models used in the analysis of fertility fluctuations since the end of [the] demographic transition. Two main families of models may be distinguished: those related to demographic 'cinematics', including the well known Easterlin model; and those related to the 'dynamics' of the reproduction system, among which Volterra's prey-predator model takes a particular place. The possibilities of operationalizing the latter model are also discussed." (SUMMARY IN ENG AND SPA)

Demography↗
PubMed1987

A clinical instrument for multi-element in vivo analysis by prompt, delayed and cyclic neutron activation using 252Cf.

The design and construction of a versatile clinical instrument for multi-element in vivo neutron activation analysis of major and minor body elements is described. A 200 micrograms (4 GBq) 252Cf neutron source is stored below ground level and pneumatically propelled to one of two irradiation ports. These deliver collimated beams of fast neutrons either to a localised volume such as the liver or kidney, or across the width of a patient for a head-to-toe scanning whole-body measurement. The source control system allows selection of either a continuous or cyclic mode of activation. The instrument is intended primarily for measurement, by the prompt-gamma technique, of total and partial body calcium, total body nitrogen and partial body cadmium. The potential of the instrument for determination of these three elements has been established. Phantom results suggest that total body calcium can be measured with a precision of +/- 2.6% (CV) for an average whole-body skin dose equivalent of 6.4 mSv; total body nitrogen with a precision of +/- 2.0% for an average whole-body skin dose equivalent of less than 0.4 mSv; and a detection limit (2 SD of the background) of 2.4 mg of cadmium in the kidney has been obtained for a radiation dose equivalent to the skin of 3 mSv (QF = 10). The suitability of this instrument for the measurement of other elements is also discussed.

Californium↗
PubMed2000

Cyclic alternating pattern and spectral analysis of heart rate variability during normal sleep.

The natural arousal rhythm of non-rapid eye movement (NREM) sleep is known as the cyclic alternating pattern (CAP), which consists of arousal-related phasic events (Phase A) that periodically interrupt the tonic theta/delta activities of NREM sleep (Phase B). The complementary condition, i.e. non-CAP (NCAP), consists of a rhythmic electroencephalogram background with few, randomly distributed arousal-related phasic events. Recently, some relation between CAP and autonomic function has been preliminarily reported during sleep in young adults by means of spectral analysis of heart rate variability (HRV). The present study was aimed at analysing the effects of CAP on HRV in a group of normal children and adolescents. Six normal children and adolescents (age range 10.0-17.5 y) were included in this study. All-night polygraphic recordings were performed after adaptation to the sleep laboratory. Six 5-min epochs were selected from sleep Stage 2 and six from Stages 3 and 4 (slow-wave sleep), both in CAP and NCAP conditions. From such epochs, a series of parameters describing HRV was then calculated, in both time and frequency domains, on the electrocardiographic R-R intervals. Statistical comparison between CAP and NCAP epochs revealed a significant difference for most of the frequency domain parameters (increase of the low-frequency band, increase of the low-frequency/high-frequency ratio and decrease in the high-frequency band during CAP) both in Stage 2 and in slow-wave sleep. Our results demonstrate that the physiological fluctuations of arousal during sleep described as CAP are accompanied by subtle, but significant, changes in balance between the sympathetic and vagal components of the autonomic system.

Adolescent↗
PubMed1996

Multiple solution conformations of the integrin-binding cyclic pentapeptide cyclo(-Ser-D-Leu-Asp-Val-Pro-). Analysis of the (phi, psi) space available to cyclic pentapeptides.

The aqueous solution structure of the cyclic pentapeptide cyclo(-Ser-D-Leu-Asp-Val-Pro-) has been determined by two-dimensional 1H-NMR spectroscopy, combined with a conformational search and distance-geometry calculations. As many as five conformers in slow exchange were observed, and the rate of interconversion between components was measured from the build-up rates of exchange peaks. NMR data allowed the structures of the two predominant conformers to be determined. The major component (66%) contained a cis-proline as part of a type-VIa2 beta-turn encompassing residues Asp-Val-cis-Pro-Ser. The second component (16%) contained only trans-amide bonds, and a type-VIII beta-turn formed by residues Val-Pro-Ser-D-Leu. These structures are discussed in relation to the (phi, psi), space available to the cyclic pentapeptide, determined by a conformational search, and in relation to previously published cyclic-pentapeptide structures. The molecule exhibits activity in a scintillation-proximity assay for the inhibition of the interaction between the integrin very-late antigen-4 (VLA-4; alpha 4 beta 1) and vascular-cell-adhesion molecule-1 (VCAM-1). The structure/activity relationship of the LDV sequence is discussed and related to the recently published X-ray structure of VCAM-1. The relevance of the work to the design of anti-inflammatory drugs is discussed.

Amino Acid Sequence↗
PubMed1980

Karyotype analysis of leukocytes of gray collie (cyclic neutropenia)-normal bone marrow transplant chimeras six years after transplantation.

Karyotype analysis was made on the leukocytes of 2 gray Collie (cyclic neutropenia)-normal bone marrow transplant chimeras transplanted 6 years previously to correct cyclic neutropenia of the gray Collie syndrome. In a male-to-female transplant chimera, all of the to metaphase spreads showed the karyotype of male donor origin. In this and the male-to-male chimera, the morphology of all chromosomes examined showed no gross anomalies or breaks which might be of recipient origin.

Agranulocytosis↗
PubMed2002

Argyrins, immunosuppressive cyclic peptides from myxobacteria. II. Structure elucidation and stereochemistry.

The structures of argyrins A-H were elucidated by NMR spectroscopy, chemical degradation and X-ray analysis as cyclic octapeptides. Argyrins A and B, in addition to the common amino acids tryptophan, glycine, dehydroalanine and alanine or alpha-aminobutyric acid, sarcosine, contain 2-(1-aminoethyl)thiazol-4-caboxylic acid and the novel amino acid 4'-methoxytryptophan. In argyrins C and D the latter is replaced by 4'-methoxy 2'-methyltryptophan. According to NMR analysis the solution and crystal conformations of argyrins A and B are identical in CDCl3 and slightly different in acetone-d6. Argyrins A and B are identical with the antibiotics A21459 A and B, whose structures are revised with respect to 4'-methoxytryptophan.

Crystallography, X-Ray↗