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Biomedical subjects

R Deslauriers

Publications and source records attributed to R Deslauriers.

At least 109 records · Page 6Linked to original sources
PubMed1980

Interaction of opioid peptides with model membranes. A carbon-13 nuclear magnetic study of enkephalin binding to phosphatidylserine.

The binding of enkephalin to phosphatidylserine has been studied, by using 13C NMR, as a model for interactions with components of biological receptors. Chemical shifts, line widths and spin-lattice relaxation times were measured for peptides enriched to 90% in 13C. The pKa values of the terminal amino and carboxyl groups were determined from the pH dependence of the 13C chemical shifts. Interaction of (2-[2-13C]glycine) methionine-enkephalin, (3-[2-13C]-glycine)methionine-enkaphalin, and (3-[2-13C]glycine)methionine-enkephalinamide with phosphatidylserine (PS) was studied as a function of pH. Salt and morphine antagonism to binding was manifest. Binding was shown to be pH dependent, exhibiting a maximum under slightly acidic conditions. Whereas the -NH3+ group of enkephalin is essential for binding, the data suggest that neither the tyrosyl hydroxyl group nor the COO- group is involved. Binding affects the 13C spin-lattice relaxation times most strongly; the chemical shifts and line widths of the 13C-enriched material show little perturbation in the presence of PS. The internal flexibility of the peptides is decreased, on binding to model membranes, by 1 order of magnitude. Dissociation constants have been measured as 4 X 10(-1) M and 2.6 X 10(-3) M for enkephalin and enkephalinamide, at pH 6.3 and 6.4, respectively.

Animals↗
PubMed1980

Degradation of enkephalin and enkephalinamide by neuroblastoma x glioma hybrid cells as studied by 13C n.m.r.

13C n.m.r. and thin-layer chromatography were used to monitor the degradation of methionine-enkephalinamide in the presence of neuroblastoma x glioma hybrid cells (NG 108-15) and membranes. Puromycin and trypsin treatment failed to protect enkephalinamide from degradation over long periods of time (up to 24 hours). The major degradation products of [3[2-13C]glycine] methionine-enkephalinamide observed by 13 C n.m.r. showed glycine-3 in a non-terminal position, an N-terminal position and free glycine. A minor component showed glycine-3 in a C-terminal position.

Cell Membrane↗
PubMed1980

31P NMR studies of vegetative and encysted cells of Acanthamoeba castellanii. Observation of phosphonic acids in live cells.

31P NMR studies have been performed on vegetative and encysted Acanthamoeba castellanii. A prominent feature of the spectra is the presence of resonances characteristic of P-C linkages. Vegetative cells show sharp phosphonate resonances whereas encysted cells show broad phosphonate resonances and narrow phosphate resonances. Studies of model compounds using 31P NMR have shown the narrow resonances to arise from 2-aminoethylphosphonic acid; the broad components from encysted cells arise from molecules with long rotational correlation times such as aggregates of lipophosphonoglycan or phosphonoprotein. Vegetative cells also show the presence of an electronegatively beta-substituted phosphonic acid, possibly 1-hydroxy-2-aminoethylphosphonic acid, a component identified in the cell membrane lipophosphoglycan. pH titration studies of a number of phosphonic acid model compounds show a chemical shift behaviour quite distinct from that of biological phosphates. Upon acidification from pH 12, resonances shift to high field followed by return to lower field at pH 1.0. These resonances can be ambiguous as monitors of cellular pH. The pH of both vegetative and encysted cells is 6.0--6.5. Encysted cells under anaerobic conditions show no spectral changes over 24 h. Vegetative cells under similar conditions show time-dependent changes characteristic of variation in cellular pH. There appears to be little correlation between pH and the variously differentiated states (vegetative or encysted) in Acanthamoeba.

Amoeba↗
PubMed1979

Cyclized dipeptide model for a beta-bend.

A cyclic dipeptide in which L-Ala-Gly was cyclized with epsilon-aminocaproic acid has been synthesized as a model for a beta-bend. Its conformational properties have been examined by means of conformational energy calculations and nuclear magnetic resonance, infrared, Raman, and circular dichroism spectroscopy in various solvents. These calculations and experiments suggest that a type II beta-bend exists in the Ala-Glymoiety, with an NH...O = C hydrogen bond in the epsilon-aminocaproic acid portion of the molecule, and that the molecule adopts a unique conformation in solution. In contrast, an open-chain analog of this compound exists in solution as an ensemble of conformations but with a significant amount of a type II beta-bend structure in the ensemble.

Circular Dichroism↗
PubMed1979

Effects of D and L amino acid residues in linear peptides on carbon-13 nuclear magnetic resonance parameters.

The 13C spectra of the linear tripeptidyl diastereoisomers, Gly-Gly-Leu, Gly-Gly-D-Leu, Leu-Gly-Gly, D-Leu-Gly-Gly, Ala3, Ala-Ala-D-Ala, Ala-D-Ala-Ala, Val3, and Val-Val-D-Val are very similar or even identical at pH meter readings of 1.0, 7.0 and 12.0 in D2O. The spectra of Pro-Leu-Gly-NH2 and Pro-D-Leu-Gly-NH2 likewise show only minor differences in 13C chemical shifts (less than 0.4 p.p.m.) under similar conditions. This contrasts significantly with previous findings comparing 13C chemical shifts of cyclo(Pro-Leu) and cyclo(Pro-D-Leu) where major differences in chemical shifts were observed for both residues due to differences in conformational constraints present in these cyclic proline-containing peptides. The least-squares fit of spin-lattice relaxation times (T1) for Pro-Leu-Gly-NH2 and Pro-D-Leu-Gly-NH2 show that it is not possible to fit all the T1 values to a unique and rigid structure whether folded or extended. The glycyl residue undergoes enhanced motion when compared with the prolyl and leucyl residues. Internal motion must be postulated within the proline ring and for the CH3 groups of leucine.

Amino Acid Sequence↗
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↗
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↗
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↗