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At least 397 records · Page 22Linked to original sources
PubMed1982

Conformational analysis of small disulfide loops. Spectroscopic and theoretical studies on a synthetic cyclic tetrapeptide containing cystine.

The conformational analysis of the synthetic peptide (formula, see text) has been carried out, as a model for small disulfide loops, in biologically active polypeptides. 1H NMR studies (270 MHz) establish that the Val(3) and Cys(4) NH groups are solvent shielded, while 13C studies establish an all-trans peptide backbone. Circular dichroism and Raman spectroscopy provide evidence for a right-handed twist of the disulfide bond. Analysis of the vicinal (J alpha beta) coupling constants for the two Cys residues establishes that chi 1 approximately +/- 60 degrees for Cys(4), while some flexibility is suggested at Cys(1). Conformational energy calculations, imposing intramolecular hydrogen bonding constraints, favor a beta-turn (type I) structure with Pro(2)-Val(3) as the corner residues. Theoretical and spectroscopic results are consistent with the presence of a transannular 4 leads to 1 hydrogen bond between Cys(1) CO and Cys(4) NH groups, with the Val NH being sterically shielded from the solvent environment.

Circular Dichroism↗
PubMed1985

Genetic analysis of the effects of morphine on plasma cyclic nucleotides and locomotor activity in male mice.

A biometric analysis of morphine-induced changes in locomotor activity and plasma cyclic nucleotide levels was conducted in two inbred strains of mice, DBA/2N and C57BL/6N, and their F1 hybrid and backcross progenies. C57BL/6N was partially dominant over DBA/2N for morphine-induced motor activity, whereas DBA/2N was partially dominant over C57BL/6N with respect to the effect of morphine on the cyclic nucleotides. The strain difference in the effect of morphine on motor activity and on plasma cyclic GMP was shown to be genetically determined, whereas the genetic influence on plasma cyclic AMP was statistically not confirmed. The number of gene pairs which regulate the effect of morphine on motor activity was assumed to be more than one; however, the contribution of more than one segregating unit in the effect of morphine on plasma cyclic GMP was not demonstrated.

Animals↗
PubMed1989

M2 subunit of ribonucleotide reductase is a target of cyclic AMP-dependent protein kinase.

Cyclic AMP arrests T lymphocytes in the G1 phase of the cell cycle, and prolonged exposure results in cytolysis. Both of these effects require cyclic AMP-dependent protein kinase. We recently observed that some S49 mouse T lymphoma cell lines selected for hydroxyurea resistance were not arrested in G1 by cyclic AMP. Further analysis revealed that these cell lines were cyclic AMP-dependent protein kinase deficient, and conversely, other cyclic AMP-dependent protein kinase deficient cell lines not selected for hydroxyurea resistance were two- to threefold more hydroxyurea resistant. However, hydroxyurea is a specific inhibitor of ribonucleotide reductase and does not inhibit this kinase. We subsequently showed that cyclic AMP-dependent protein kinase will phosphorylate the M2 but not the M1 subunit of ribonucleotide reductase in vitro, and this phosphorylation will diminish CDP reductase activity. In vivo phosphorylation of M2 occurred under conditions similar to those that generate cell cycle arrest. We conclude that the M2 subunit of ribonucleotide reductase can be a target of cyclic AMP-dependent protein kinase. The phosphorylated enzyme has diminished activity, and this may play a role in cyclic AMP-induced lymphocyte cell cycle arrest.

Animals↗
PubMed1990

Effects of cyclic GMP on the secondary structure of cyclic GMP dependent protein kinase and analysis of the enzyme's amino-terminal domain by far-ultraviolet circular dichroism.

Far-UV circular dichroism spectra of bovine lung cyclic GMP dependent protein kinase (G-kinase) show that the enzyme contains alpha-helical and beta-pleated sheet elements. Binding of cyclic GMP changes the spectra in a way consistent with the induction of beta-sheet from random coil. Examination of the amino-terminal sequence of G-kinase indicates the presence of a strongly alpha-helical segment with several features in common with the leucine zipper motif. We propose that this sequence may be the important part of the dimerization domain of the enzyme. A synthetic peptide corresponding to amino acids 1-39 of G-kinase has a strongly alpha-helical CD spectrum, supporting the predicted secondary structure of this amino-terminal sequence. In contrast to the native enzyme, a structure reduced in alpha-helix was found when a constitutively active form of G-kinase, which lacks amino acids 1-77, was studied.

Allosteric Site↗
PubMed1978

Changes in plasma luteinizing hormone-releasing hormone and gonadotropin concentrations during constant rate intravenous infusion of luteinizing hormone-releasing hormone in cyclic rats.

Further analysis has been made of the response of the rat pituitary gland to LHRH during the 4-day estrous cycle. LHRH was infused iv at a constant rate (50 ng/h) into phenobarbital-treated rats at different times during the estrous cycle. Infusion at this rate in proestrous rats simulates the rising and plateau phases of the spontaneous proestrous surges of LH and FSH in plasma. Plasma LH rose to similar heights during the "initial phase" of LH release (during the first 40 min of infusion) on the afternoons of estrus, diestrous day one, and proestrus and during the morning of proestrus. The increase during the afternoon of diestrous day two was significantly less than that in all the other groups. A similar response was seen in the case of FSH release. A "rapid rising" or "augmented" phase of LH release (during 40-120 min of infusion) was present in all groups and the magnitude of the response was greatest during the afternoon of proestrus. In the case of FSH, an augmented phase of release started 60 min after the start of infusion, and the response during the afternoon of proestrus was slightly greater than the responses measured at the other times tested. The responses on diestrous day one were not altered when phenobarbital was omitted or when rats were ovariectomized shortly before LHRH infusion. Other differences in the LH and FSH responses during both initial and augmented phases of release were seen in rats tested at different times during the estrous cycle with an LHRH infusion rate which caused a supraphysiological response on proestrus. The results suggest that 1) the initial rising phases in plasma LH and FSH during the spontaneous surges during proestrus are not the result of an increase in pituitary responsiveness to LHRH during the estrous cycle, 2) augmented phases of LH and FSH release can be elicited on all days of the estrous cycle, and 3) the increases in magnitude of the augmented phases of LH and FSH release on proestrus, as compared to those on other days of the cycle, are the result of an increase in pituitary responsiveness to LHRH during the estrous cycle.

Animals↗
PubMedDate not supplied

Phase transfer catalysis in solid phase peptide synthesis. Preparation of cyclo[Xxx-Pro-Gly-Yyy-Pro-Gly] model peptides and their conformational analysis.

Relatively small cyclic peptides that contain functionalized side chains provide interesting model compounds for studying side chain-side chain interactions, peptide backbone flexibility (especially if X-Pro bonds are included), and as potential enzyme mimetics. In order to develop more efficient synthetic routes to compounds such as cyclo(Xxx-Pro-Gly-Yyy-Pro-Gly), using the Merrifield method, we have investigated several orthogonal solid phase synthesis strategies and contrasted the use of two solid phase peptide-resin cleavage techniques for preparing partially protected linear sequences. Phase transfer catalysis using tetrabutyl ammonium hydrogen sulfate in THF with saturated aqueous K2CO3 provides peptide acid salts in which most of the common protecting groups (Arg(NO2), Tyr(Bzl), Z-Lys, Lys(Boc), and Glu(tBu)) are not affected. Using 500 MHz proton NMR, peptides having a cyclo (L-L-Gly-L-L-Gly) sequence generally display two conformers in DMSO-d6 with the major isomer being the bis-cis conformer, while the minor form contains two beta turns. For peptides with a cyclo(D-L-Gly-L-L-Gly) sequence, the major conformer contains one cis and one trans X-Pro bond and one Type II beta turn, as previously predicted for related structure by Kopple and others.

Catalysis↗
PubMed2001

NMR solution structure and conformational analysis of the calcium release agent cyclic adenosine 5'-diphosphate ribose (cADPR).

A high-resolution NMR study of the solution structure of the calcium release agent cADPR has been performed. Pseudorotationals analysis reveals that in solution both sugar rings in cADPR adopt predominantly (approximately 75%) South conformations, with the A and N rings adopting approximately 2T3 (C2'-endo(major)-C3'-exo(minor) and 4(3)T (C3'-exo-C4'-endo) conformations, respectively. The backbone torsion angles beta and gamma have also been determined. While the minor North conformers were not observed in the crystal structure of cADPR, the solution values of the major South conformers compare well to those found in crystal structure.

Adenosine Diphosphate Ribose↗
PubMed1998

Scanning electron microscopic and morphometric analysis of the guinea pig uterine luminal surface: cyclic and ovarian steroid-induced modifications.

A morphometric and scanning electron microscopic analysis of endometrial, luminal topographical changes of cyclic and ovariectomized, ovarian steroid-treated guinea pigs was undertaken to determine the effects of cyclic endocrine influences on the uterine surface features recognized to be involved in the process of interstitial blastocyst implantation. Estrogenic stimulation of the uterine epithelial layer induced microvillus growth and closed the endometrial gland openings on the luminal surface. Progestins antagonized these parameters, as indicated by short, sparse microvillus formation over a flat luminal uterine surface on which gland openings were both numerous and prominent. The combined effects of estrogen and progesterone therapies induced luminal epithelial changes resembling those characterizing the cyclic uterine surface at the time of blastocyst implantation. These data indicate that the cyclic alterations in the uterine luminal surface are directly regulated by ovarian steroid hormones, and that these changes in surface structure are synchronized and directly involved in the preparation for blastocyst-uterine interaction during the nidatory process in this species.

Animals↗
PubMed1992

Human bronchial cyclic nucleotide phosphodiesterase isoenzymes: biochemical and pharmacological analysis using selective inhibitors.

1 The aims of the present study were to characterize the cyclic nucleotide phosphodiesterase (PDE) isoenzyme activities present in human bronchi and to examine the ability of selective isoenzyme inhibitors to relax histamine and methacholine precontracted preparations of human bronchi. 2 Three separations of pooled human bronchial tissue samples were performed. Ion-exchange chromatography showed that the soluble fraction of human bronchial preparations contains PDE I, II, III, IV and V isoenzyme activities. Multiple forms of PDE I and PDE IV were observed and PDE IV was the main cyclic AMP hydrolytic activity. 3 3-Isobutyl-l-methylxanthine (IBMX) non-selectively inhibited all separated isoenzyme activities. Zaprinast selectively inhibited PDE V, but also effectively inhibited one of the two PDE I isoforms identified. The PDE IV selective inhibitors rolipram and RO-201724, inhibited the PDE IV activities as did the dual PDE III/IV inhibitor, Org 30029. Org 9935, a PDE III selective inhibitor, potently attenuated part of the PDE IV activity peak in one of three separations performed, indicating that some PDE III activity may co-elute with PDE IV under the experimental conditions employed. 4 PDE IV-selective (rolipram), PDE III-selective (Org 9935) and dual PDE III/IV (Org 30029) inhibitors were effective relaxants of human bronchial smooth muscle. The PDE V/PDE I inhibitor, zaprinast was relatively ineffective. 5 The present study demonstrates in human bronchi, as in animal airways smooth muscle, that inhibitors of PDE III, PDEIV and dual PDE III/IV have potentially useful bronchodilator activity and are worthy of further consideration as anti-asthma drugs.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

[Clinical gait analysis--methods, limitations and possible applications].

Human gait is a complex and cyclic movement. Gait analysis of human walking can be done either without any technical support, or in combination with complex and expensive equipment. Modern gait analysis is based on the integration of multiple components to derive a complete analysis of gait. These methods may include observation, videotaping, electromyography, kinematics, kinetics and energetics. The results gained from these methods may then be used to determine the treatment course of a subject with gait abnormalities or to document the effects of therapeutical intervention. The purpose of this article is to provide an overview of the most common used methods in gait analysis. Emphasis will be placed on the type of information that can be derived from each component and how this information can be used clinically.

Electromyography↗
PubMed2003

Morphological analysis of the hyperpolarization-activated cyclic nucleotide-gated cation channel 1 (HCN1) immunoreactive bipolar cells in the rabbit retina.

Hyperpolarization-activated cation currents (I(h)) have been identified in neurons in the central nervous system, including the retina. There is growing evidence that these currents, mediated by the hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN), may play important roles in visual processing in the retina. This study was conducted to identify and characterize HCN1-immunoreactive (IR) bipolar cells by immunocytochemistry, quantitative analysis, and electron microscopy. The HCN1-IR bipolar cells were a subtype of OFF-type cone bipolar cells and comprised 10% of the total number of cone bipolar cells. The axons of the HCN1-IR cone bipolar cells ramified narrowly in the border of strata 1 and 2 of the inner plexiform layer (IPL). These cells formed a regular distribution, with a density of 1,825 cells/mm(2) at a position 1 mm ventral to the visual streak, falling to 650 cells/mm(2) in the ventral periphery. Double-labeling experiments demonstrated that their axons stratified narrowly within and slightly proximal to the OFF-starburst amacrine cell processes. In the IPL, they were presynaptic to amacrine cell processes. The most frequent postsynaptic dyads formed of HCN1-IR bipolar cell axon terminals are pairs composed of both amacrine cell processes. These results suggest that these HCN1-IR cone bipolar cells might be the same as the DAPI-Ba1 bipolar population, and might therefore be involved in a direction-selective mechanism, providing inputs to the OFF-starburst amacrine cells and/or the OFF-plexus of the ON-OFF ganglion cells.

Amacrine Cells↗
PubMed1996

Distinct conformational preferences of three cyclic beta-casomorphin-5 analogs determined using NMR spectroscopy and theoretical analysis.

The conformational properties of three cyclic beta-casomorphin analogs based on the general formula H-Tyr-c[-D-Orn-2-Nal-D-Pro-Xaa-] (2-Nal = 2-naphthylalanine; Xaa = D-Ala, Sar or NMe-Ala) in DMSO solution were investigated using NMR spectroscopy in conjunction with molecular modeling techniques. The D-Ala5- and Sar5-analogs (compounds 1 and 2 respectively) are potent mixed mu-agonist/delta-antagonists with high mu- and delta-opioid receptor affinities, whereas the NMe-Ala5-analog (compound 3) is a potent mu-agonist and a weak partial delta-agonist. Distinct conformational differences emerged for the three compounds studied. Flexibility in the bare ring structures was found to increase in the order 3 < 2 < 1. The increased structural rigidity of 3 may be responsible for its low delta-receptor affinity as compared to the two other analogs. A low fractional population of conformers containing two cis peptide bonds was found for compound 2 but not for analog 1 or 3. Initial evidence for this observation was obtained from NMR differential line-broadening experiments and later confirmed by molecular mechanics simulations. Comparison of the temperature dependence of amide proton chemical shifts acquired for the three cyclic analogs indicate a large degree of intramolecular hydrogen bonding for 1 but not for the other two peptides.

Endorphins↗
PubMed2001

New cyclic depsipeptide antibiotics, clavariopsins A and B, produced by an aquatic hyphomycetes, Clavariopsis aquatica. 2. Structure analysis.

The structures of new cyclic decadepsipeptides, clavariopsins A and B, were determined to be cyclo[-(R)-2-hydroxyisovaleryl-L-pipecoyl-L-MeVal-L-Val-L-MeAsp-L-MeIle-L-MeIle-Gly L-MeVal-L-Tyr(OMe)-] and cyclo[-(R)-2-hydroxyisovaleryl-L-pipecolyl-L-Val-L-Val-L-MeAsp-L-Melle-L-MeIle-Gly-L-MeVal-L-Tyr(OMe)-], respectively, by spectroscopic analyses, especially using 2D NMR techniques. The absolute stereochemistry was elucidated by the advanced Marfey's method and chiral HPLC analysis.

Anti-Bacterial Agents↗
PubMed1989

Cystine peptides. Antiparallel beta-sheet conformation of the cyclic biscystine peptide [Boc-Cys-Ala-Cys-NHCH3]2.

The crystal structure analysis of the cyclic biscystine peptide [Boc-Cys1-Ala2-Cys3-NHCH3]2 with two disulfide bridges confirms the antiparallel beta-sheet conformation for the molecule as proposed for the conformation in solution. The molecule has exact twofold rotation symmetry. The 22-membered ring contains two transannular NH...OC hydrogen bonds and two additional NH...OC bonds are formed at both ends of the molecule between the terminal (CH3)3COCO and NHCH3 groups. The antiparallel peptide strands are distorted from a regularly pleated sheet, caused mainly by the L-Ala residue in which phi = -155 degrees and psi = 162 degrees. In the disulfide bridge C alpha(1)-C beta(1)-S(1)-S(3')-C beta(3')-C alpha(3'), S--S = 2.030 A, angles C beta SS = 107 degrees and 105 degrees, and the torsional angles are -49, -104, +99, -81, -61 degrees, respectively. The biscystine peptide crystallizes in space group C2 with a = 14.555(2) A, b = 10.854(2) A, c = 16.512(2) A, and beta = 101.34(1) with one-half formula unit of C30H52N8O10S4.2(CH3)2SO per asymmetric unit. Least-squares refinement of 1375 reflections observed with magnitude of F greater than 3 sigma(F) yielded an R factor of 7.2%.

Amino Acid Sequence↗
PubMed1998

[Analysis of alpha-Oxo ketene cyclic dithioacetals compounds by using Kalman filtering and UV spectrophotometry].

The Kalman filtering and UV spectrophotometry have been used to analyte the alpha-Oxo ketene cyclic dithioacetal compounds in the present paper. The innovation sequence and concentration trends in the Kalman filtering process have been investigated, results show that the combination of the Kalman filtering and UV spectrophotometry is an applicable and reliable means in analysis of this kind of compounds.

English Abstract↗
PubMed1996

Analysis of the spacer DNA between the cyclic AMP receptor protein binding site and the lac promoter.

The role of the spacer region DNA between the cyclic AMP receptor protein (CRP) site and the RNA polymerase in the lac promoter was examined. We wanted to determine whether the wild-type DNA sequence of this region was an absolute requirement for CRP activation of lac transcription. The sequence of a 9-bp stretch of the spacer, from -41 to -49 relative to the start of transcription, was randomized, and the effect of randomization on lac expression was investigated in vitro and in vivo. We found that the spacer contains no specific sequence determinants for CRP activation of lac transcription; fewer than 1% of the mutants displayed greater than a 50% decrease in CRP activation of lac transcription.

Bacterial Proteins↗