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R Lazaro

Publications and source records attributed to R Lazaro.

32 records · Page 2Linked to original sources
PubMed1989

Ionic pores formed by cyclic peptides.

It is shown that 2 cyclic tetrapeptides, namely tentoxin and HC toxin, are able to induce the formation of transmembrane ionic channels, although a carrier mechanism could be expected on the basis of their chemical structure (presence of proline or N-methylated residues). Since other cyclic peptides but of larger size, i.e., tyrocidines, gramicidin S (decapeptides) and an octapeptide with a sequence similar to that of HC toxin, are also able to form pores, it appears that this property can be extended to a large number of cyclic peptides. A pore structure based on aggregates is proposed.

Circular Dichroism↗
PubMed1989

Gramicidin A analogs: influence of the substitution of the tryptophans by naphthylalanines.

The synthesis of 4 linear gramicidins bearing both polar and non-polar aromatic side chains is described. From the single channels data, it appears that the relative positions of these residues has little or no influence on the conductance and that this conductance is governed mainly by the number of tryptophan residues. It is also shown that the effect of the bulkiness of the apolar aromatic side chain can be neglected.

Alanine↗
PubMed1989

Conformations, cation binding, and transmembrane ion transfer properties of a cyclooctapeptide built by an alternation of D and L residues.

The conformations of a cyclic octapeptide built with an alternation of D and L residues are investigated on the basis of 1H n.m.r. and CD data. The cyclooctapeptide can form structures which are specific to the alternating D-L sequence. This peptide can form two types of complexes with cations (peptide 2-cation and peptide-cation complexes) and the binding with monovalent cation is weak. This peptide is able to induce transmembrane ion transfer through both a carrier mechanism and pore formation.

Acetonitriles↗
PubMed1989

Synthesis and ionic channels of a linear gramicidin containing naphthylalanine instead of tryptophan.

Naphthylalanine gramicidin A was prepared by the solid phase method using an aminopolyacrylic resin after optical resolution of (D, L) naphthylalanine by enzymatic methods. Removal of the peptide from the resin was achieved by transesterification of the succinic ester linkage. Infrared spectroscopy indicated that the presence of naphthylalanine strongly modifies the monomer-dimer equilibrium. Single-channel measurements suggested that the conductance of the gramicidin channel can be governed by the dipole moment of the aromatic side-chains.

1-Naphthylamine↗
PubMed1987

Synthesis of HC toxin and related cyclopeptides containing the (L-Ala-D-Ala-L-Ada-D-Pro) sequence.

In studies leading to HC toxin synthesis, a phytotoxic cyclic tetrapeptide with the sequence cyclo (L-Ala-D-Ala-L-Aoe-D-Pro), we have determined optimal conditions for the cyclization which constitutes one of the most important steps in the synthesis of the toxin. All four possible sequences containing an optically active precursor, i.e. L-Ada = (2 S)-2-amino-9-decenoic acid instead of Aoe, have been prepared and subjected to cyclization. Owing to the differences in racemization risk during activation of the terminal carboxyl aminoacid different cyclization procedures have been applied. Cyclopeptide yields and selectivity between cyclomonomer and dimer both containing the title sequence are mainly controlled by the linear precursor sequence. The cyclic tetrapeptide is only obtained with D-proline in the C-terminal position, the best yield reached by the -ONSu activation method. Starting from the peptide, the (9S, 9R) HC toxin epimer on the epoxidic carbon atom has been further synthesized in two steps.

Amino Acid Sequence↗
PubMed1987

Cyclic tetrapeptides with sequences related to HC toxin. Conformations and cation binding.

Peptides with sequences related to HC toxin (cyclo(LAla-DAla-L-Aoe-DPro] can adopt a conformation locked by three gamma turns. A "structure--spectroscopy characteristics" relationship is proposed. These peptides can complex Mg++ cations and the binding is accompanied by a transconformation of the peptide backbone. The relevance with the biological activity of the toxin is discussed.

Amino Acid Sequence↗
PubMed1983

Azidocalmodulin derivatives. Activation of, and binding to, three target proteins: aorta myosin light-chain kinase, erythrocyte (Mg2+ + Ca2+)-dependent ATPase and cardiac sarcoplasmic-reticulum kinase.

Different azidocalmodulin derivatives were synthesized by modification of either one carboxylic acid group or one or several arginine residues and their binding and activation capacity investigated in three target enzyme systems. The systems studied were smooth-muscle myosin light-chain kinase, cardiac sarcoplasmic-reticulum kinase and erythrocyte (Mg2+ + Ca2+)-dependent ATPase. The results indicated that the activation ability of each calmodulin derivative was different depending on the system studied. Binding studies carried out by the displacement of 125I-calmodulin indicated that the monosubstitutions did not greatly alter the apparent Kd of calmodulin for the enzymes but that the modification of four arginine residues caused a 4-8-fold increase in the apparent Kd in all systems. These results have shown that azidocalmodulin derivatives may have different degrees of usefulness in the study of calmodulin target proteins in different systems, with the behaviour of the derivatives not predictable on the basis of the nature (soluble or membrane-bound) or the type (ATPase or kinase) of enzyme system to be investigated. However, the monosubstituted calmodulin and, in particular, the carboxylic acid-group-modified derivative (where the modification was statistically dispersed over the protein chain) are good candidates for photolabelling calmodulin-binding proteins.

Amino Acids↗
PubMed1982

Gold toxicity presenting as peripheral neuropathy.

A patient with rheumatoid arthritis developed gold induced peripheral neuropathy after 255 mgs of aurothioglucose. This neuropathy is characterized by weakness and numbness of the hands and feet in association with hyperalgesia of the palmar surface of the hands. The absence of vasculitis permits differentiation of gold neuropathy from the neuritis associated with rheumatoid arthritis or systemic lupus erythematosus. Treatment consists in cessation of gold and possibly the use of dimercaprol; recovery is slow but generally complete.

Adult↗
PubMedDate not supplied

Antitumoral cyclic peptide analogues of chlamydocin.

A series of cyclic tetrapeptides bearing the bioactive alkylating group on an epsilon-amino-lysyl function have been examined for their antitumoral activity on L1210 and P388 murine leukemia cell lines. One analogue belonging to the chlamydocin family and bearing a beta-chloroethylnitrosourea group was found to be potent at inhibiting L1210 cell proliferation and had a higher therapeutic index than the reference compound bis-beta-chloroethylnitrosourea (BCNU) on the in vivo P388-induced leukemia model.

Amino Acid Sequence↗
PubMedDate not supplied

Soluble polymer supported synthesis of alpha-amino acid derivatives.

A Schiff base activated glycine supported on a soluble polymer (poly(ethylene glycol) (PEG)) was readily alkylated with a wide variety of electrophiles in the presence of a carbonate base in acetonitrile. The presence of the polymer provided a phase-transfer catalysis environment which accelerated the reaction. Effects of various carbonate bases and leaving groups have been also studied. Completion of the PEG-supported reaction was obtained without using a large excess of reagents or an extra phase-transfer catalyst, even in the case of unreactive or hindered electrophiles. After cleavage from the polymer, alpha-amino esters are obtained in good yields.

Alkylation↗
PubMedDate not supplied

The effect of commercial processing on incurred residues of DDE in meat products.

The influence of processing on the degradation of DDE in meat products was investigated. First, the current level of contamination in six different types of Spanish meat products was determined. Analysis were carried out by capillary gas chromatography with electron capture detector. Of the three residues analysed (both o,p' and p,p' isomers of DDT, DDD, and DDE), only p,p'-DDE was found above the detection limit of 4 micrograms/kg fat. The frequency of p,p'-DDE detection for the various products investigated varied between 78 and 100% of the 129 samples analysed, although mean levels were very low, in the range within 6-16 micrograms/kg. No sample contained DDE residues above the EC maximum residue limit of 1 mg/kg for DDT and metabolites on meat products. Mean concentrations of DDE in Spanish meat products have declined since 1980 by more than 10-fold as compared with previously reported data. Meat products following three commercial processes were analysed to compare the levels of DDE in the finished products with those obtained in the starting material. The average levels of DDE remained unchanged after 30 days of curing in 26 samples of pork sausage. Similarly, mean DDE concentrations were essentially constant throughout the ripening process to which 30 hams were subjected. Finally, cooking in an oven (80-82 degrees C for 100 min) of 20 pork bologna samples produced an apparent increase of 12.5% in mean p,p'-DDE levels that was not statistically significant (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Use of erythropoietin in emergencies: massive intoxication by chloramines.

Recombinant human Erythropoietin (rHuEPO) is normally used to correct anaemia in patients with End Stage Renal Disease (ESRD), that are in Regular Dialysis Treatment (RDT). This anaemia is usually due to the existence of two factors: A decrease in the erythropoiesis of the bone marrow and an increase in peripheral haemolysis and, consequently, a decrease in the life span of the red cells.

Anemia↗