PubMed Health⌕ Search

Biomedical subjects

F Reig

Publications and source records attributed to F Reig.

54 records · Page 3Linked to original sources
PubMed1989

Conformation-activity relationship in hexapeptides related to substance P.

Two hexapeptides related to the undecapeptide substance P (SP) Glu-Phe-Phe-Gly-Leu-Met-NH2 and Glu-Phe-Phe-Pro-Leu-Met-NH2, have been synthesized and their selectivity for the SP receptors studied. Conformational analyses of both peptides have been carried out using a molecular modeling program. Activity appears to be related to the adoption of a U-shape conformation since the Pro9 containing peptide in which this folding is favoured is much more active than the hexapeptide containing Gly9. Moreover, such a substitution induces a significant selectivity for the SP-P receptor compared to the SP-E receptor.

Animals↗
PubMed1988

Kinetic study of alpha-chymotrypsin-catalyzed synthesis of kyotorphin.

A kinetic analysis of reaction-rate data obtained during a series of optimization experiments of the alpha-chymotrypsin-catalyzed synthesis of kyotorphin has been performed. The kinetic data have been fitted to a model equation derived from a proposed sequential mechanism, which has been further simplified to a first-order equation as a function of the substrate consumption. Statistical tests performed validate the model, since the fitted constants were statistically significant. In addition, the activation energy of the process has been calculated and resulted to be 32.5 +/- 2.3 kJ/mol which is within the range of other enzymatic reactions.

Chymotrypsin↗
PubMed1988

A physicochemical study of the interaction of phosphatidylinositol with buprenorphine and naloxone.

The interactions of two opioid molecules (buprenorphine and naloxone) with phosphatidylinositol and phosphatidylcholine were studied in lipid monolayers at the air-water interface. The influence of Na+, Ca2+, and Mn2+ ions in these interactions has also been determined. Neither buprenorphine nor naloxone influence the ordered state of phosphatidylcholine monolayers. On the contrary, both opioid molecules interact specifically with phosphatidylinositol monolayers. The area/molecule of phosphatidylinositol spread on buprenorphine containing subphases is highly affected by this molecule and also by ions. The phosphatidylinositol/naloxone interactions are rather weak and less affected by ions.

Buprenorphine↗
PubMed1988

[D-Met2,Pro5] enkephalin [N1.5-beta-D-glucopyranosyl] amide: a glycosylpeptide with high antinociceptive activity.

Different synthetic strategies have been attempted for the synthesis of a glycosylpeptide resulting from the covalent bonding of a sugar residue to the C-terminal carboxyl group of an enkephalin related pentapeptide. The final structure is: Tyr-D-Met-Gly-Phe-Pro [N1.5-beta-D-glucopyranosyl] amide. The in vitro potency on the GPI test of this analogue was IC50 = 64.0 nM. However, its antinociceptive activity by tail immersion tests, after intraperitoneal administration, was 2000 and 200 times higher than morphine in rats and mice, respectively.

Analgesics↗
PubMed1987

Kinetically controlled enzyme-catalyzed synthesis of kyotorphin. An optimization study.

Regarding the alpha-chymotrypsin-catalyzed synthesis of Z-Tyr-Arg-NH2, the effect on the reaction yield of the following experimental factors is discussed: DMF/buffer proportions, reaction temperature, and donor/nucleophile ratios. The experimental design shows that relatively better yields are obtained by increasing the reaction temperature and lowering the cosolvent proportion while maintaining a slight excess of nucleophile. The ascensional line reaches an optimal response surface very flat voided of a well-defined maximum.

Analgesics↗
PubMed1985

Interaction of morphine and naloxone with mixed monolayers of lecithin and gangliosides.

Monomolecular films of lecithin, gangliosides or lecithin/gangliosides mixtures were studied on a Langmuir through in order to examine the interactions between these lipids and opioid agonists or antagonists. Lecithin alone did not interact in a monolayer structure with opioids. However, gangliosides and lecithin/gangliosides mixtures were expanded by both morphine and naloxone. The expansion of ganglioside-containing monolayers was greater with morphine than with the antagonist, naloxone.

Chemical Phenomena↗
PubMedDate not supplied

Insertion of MAP4-VP1 peptide into lipid monolayers and bilayers.

Myscibility of dipalmitoylphosphatidylcholine (DPPC) with dipalmitoylphosphatidylglycerol (DPPG), cardiolipine (CL) and dipalmitoylphosphatidylethanolamine (DPPE) was studied using monomolacular layers of different compositions. The influence of MAP4-VP1 peptide construct related to HAV protein in mixed monolayers of the above cited lipid components was determined following penetration kinetics and compression isotherms. Moreover, liposomes with the same composition as monolayers were saturated with ANS or DPH and incubated with MAP4VP1, and polarization values as well as transition temperatures were determined. In general interaction is maximum with DPPC/DPPG mono and bilayers, followed by DPPC/CL. In these systems electrostatic repulsive forces seem to play a strong role.

1,2-Dipalmitoylphosphatidylcholine↗
PubMedDate not supplied

Effect of a laminin amphiphatic sequence on DPPC ordered bilayers.

A peptide sequence, stearoyl-GESIKVAVS(NH2), related to a laminin fragment, has been synthesized. Formation of aggregates was controlled by titrating a sodium anilinonaphthalene sulphonate (ANS) solution with peptide and recording fluorescence intensity increases. The results show that this system experiences a sudden increase in fluorescence at peptide concentrations around 2.5 x 10(-4) mol/L. The interaction of this hydrophobic peptide with DPPC vesicles has been studied using fluorescence techniques. Its influence on the microviscosity of bilayers was determined by studying polarization/temperature dependence for ANS and diphenyl hexatriene (DPH) fluorescent probes. With both markers the presence of peptide promotes a clear increase in anisotropy values. This indicates a rigidifying effect. Leakage studies carried out with liposomes loaded with carboxyfluorescein (CF) indicate a stabilizing effect of the peptide on bilayers, in agreement with results obtained with fluorescent probes.

1,2-Dipalmitoylphosphatidylcholine↗
PubMedDate not supplied

Biological activity of Leu-enkephalin containing hydrophobic moieties.

A series of enkephalin analogues (Tyr-Gly-Gly-Phe-Leu-C-NH-R;R=C6,C8,C10,C12 and C14; C=CH2 groups) with increasing hydrophobic character have been tested behaviourally in the analgesic hot plate and tail flick tests. The analogues were administered intraperitoneally and were found to possess anti-nociceptive activity. The results indicate that apparently there is not a direct relationship between increasing hydrophobicity and activity of the enkephalin-alkyl-amide analogues. The enkephalin analogues were found to behave in the same way as the enkephalins in producing tolerance.

Analgesia↗
PubMedDate not supplied

Evaluation of free and liposome-encapsulated gentamycin for intramuscular sustained release in rabbits.

Gentamycin sulphate (GS) and gentamycin oleate (GO) were encapsulated in liposomes composed of phosphatidylcholine (HPC) and cholesterol (CHOL) (molar ratio 7:7:2 and 5:5:1, respectively), and were administered via intramuscular injection to rabbits, to evaluate their potential use as sustained release formulations. Five groups of five animals each were used for the pharmacokinetic study, and treatments were established as follows: 3 mg kg(-1) of GS i.v., 3 mg kg(-1) of GS i.m., 3 mg kg(-1) of liposome-containing gentamycin sulphate (LGS) i.m., 3 mg kg(-1) of GO i.m., and 3 mg kg(-1) of liposome-containing gentamycin oleate (LGO) i.m. Gentamycin plasma concentrations after i.m. administration of LGS were extremely low compared with those obtained after the i.m. administration of GS; the peak plasma concentration (Cmax) showed an eight-fold decrease with LGS, and the area under the concentration-time curve (AUC) was four-fold lower for the liposomal form. The apparent elimination half-life estimated after administration of LGS showed a three-fold increase compared with values calculated for free GS. After the administration of the same dose of LGO, Cmax obtained showed a 2.5-fold decrease in relation to peak concentrations of free GO, and the apparent beta-half life of encapsulated GO showed a three-fold increase compared with i.m. GO. Large-size liposomes containing gentamycin administered i.m. to rabbits gave sustained drug release from the injection site, providing prolonged plasma concentrations of the drug in the body.

Animals↗
PubMedDate not supplied

Phospholipid-model membrane interactions with branched polypeptide conjugates of a hepatitis A virus peptide epitope.

To establish correlation between structural properties (charge, composition, and conformation) and membrane penetration capability, the interaction of epitope peptide-carrier constructs with phospholipid model membranes was studied. For this we have conjugated a linear epitope peptide, (110)FWRGDLVFDFQV(121) (110-121), from VP3 capside protein of the Hepatitis A virus with polylysine-based branched polypeptides with different chemical characteristics. The epitope peptide elongated by one Cys residue at the N-terminal [C(110-121)] was attached to poly[Lys-(DL-Ala(m)()-X(i)())] (i < 1, m approximately 3), where x = ø(AK), Ser (SAK), or Glu (EAK) by the amide-thiol heterobifunctional reagent, 3-(2-pyridyldithio)propionic acid N-hydroxy-succinimide ester. The interaction of these polymer-[C(110-121)] conjugates with phospholipid monolayers and bilayers was studied using DPPC and DPPC/PG (95/5 mol/mol) mixture. Changes in the fluidity of liposomes induced by these conjugates were detected by using two fluorescent probes 1,6-diphenyl-1,3, 5-hexatriene (DPH) and sodium anilino naphthalene sulfonate (ANS). The binding of conjugates to the model membranes was compared and the contribution of the polymer component to these interactions were evaluated. We found that conjugates with polyanionic/EAK-[C(110-121)] or polycationic/SAK-[C(110-121)], AK-[C(110-121)]/character were capable to form monomolecular layers at the air/water interface with structure dependent stability in the following order: EAK-[C(110-121)] > SAK-[C(110-121)] > AK-[C(110-121)]. Data obtained from penetration studies into phospholipid monolayers indicated that conjugate insertion is more pronounced for EAK-[C(110-121)] than for AK-[C(110-121)] or SAK-[C(110-121)]. Changes in the fluorescence intensity and in polarization of fluorescent probes either at the polar surface (ANS) or within the hydrophobic core (DPH) of the DPPC/PG liposomes suggested that all three conjugates interact with the outer surface of the bilayer. Marked penetration was documented by a significant increase of the transition temperature only with the polyanionic compound/EAK-[C(110-121)]. Taken together, we found that the binding/penetration of conjugates to phospholipid model membranes is dependent on the charge properties of the constructs. Considering that the orientation and number of VP3 epitope peptides attached to branched polypeptides were almost identical, we can conclude that the structural characteristics (amino acid composition, charge, and surface activity) of the carrier have a pronounced effect on the conjugate-phospholipid membrane interaction. These observations suggest that the selection of polymer carrier for epitope attachment might significantly influence the membrane activity of the conjugate and provide guidelines for adequate presentation of immunogenic peptides to the cells.

1,2-Dipalmitoylphosphatidylcholine↗
PubMedDate not supplied

Preparation and in vitro activity of liposome encapsulated opioids.

Four opiate molecules: morphine, naloxone, meperidine and codeine have been encapsulated in liposomes. The encapsulation efficiency has been studied as a function of the following parameters: liposome preparation method, lipid composition and opioid molecule hydrophobicity. The most important parameter as far as the entrapment efficiency is concerned is the liposome preparation method. The opioid activity of these molecules in vitro (Guinea Pig Ileum preparation) has been determined. No differences in the IC50 values could be found between encapsulated and free drug molecules.

Animals↗