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Query: Y22D7AL .14
 53,079 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synthesis and pharmacological potencies of oxytocin and lysine-vasopressin analogues are reported in which the N5-amide of their glutaminyl residues are dialkylated. These analogues have been studied as an ongoing exploration of the biological effects on the natural hormones of substituting individually one of the amino acid residues, which has a hydrophilic side chain and which are thought to be part of the hydrophilic surface of the hormones. [4-(N5,N5-Dimethylglutamine)]oxytocin (17), [4-(N5,N5-di-n-propylglutamine)]oxytocin (18), and [4-(N5,N5-dimethylglutamine)] lysine-vasopressin (19) were synthesized by clasical solution techniques. Potencies in the in vitro rat uterotonic, avian vasodepressor, rat pressor, and rat antidiuretic assays were determined and are as follows, respectively: for compound 17 3.01 +/- 0.14 units/mg, 4.55 +/- 0.03 units/mg, tachyphylaxis and tachyphylaxis; for compound 18 less than 0.1, less than 0.1, less than 0.05, and less thad 1.88 +/- 0.04 units/mg. The potencies in all cases are significantly less than those of the parent hormone. The results are discussed in terms of the proposed biologically active conformations of the hormones at the uterotonic receptor and at the antidiuretic receptor.
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PMID:Oxytocin and lysine-vasopressin with N5,N5-dialkylglutamine in the 4 position: effect of introducing sterically hindered groups into the hydrophilic cluster of neurohypophyseal hormones. 735 37

The chemical composition of five samples of Iraqi mung beans chosen from different geographical regions were investigated as well as their amino acid contents. The results indicated that all the samples were good sources of protein, carbohydrates and minerals. They contained 24.95-28.04% protein, 64,15-66.32% carbohydrates, 0.86-0.96% crude fat, 3.37-4.05% ash and 4.13-5.01% crude fibre. The amounts of phosphorus, calcium and iron were within the ranges; 381-528, 128-143 and 5.14-5.76 milligrams per 100 grams of flour, respectively (all results on a dry weight basis). Further, all samples were rich in most essential amino acids, especially lysine (5.85-8.24 grams per 100 grams of protein) but they were deficient in methionine (0.96-1.48 gram per 100 grams of protein).
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PMID:Chemical and amino acid composition of Iraqi mung beans. 744 57

Although the interaction of proteins with glycosaminoglycans (GAGs) such as heparin are of great importance, the general structural requirements for protein- or peptide-GAG interaction have not been well characterized. Electrostatic interactions between sulfate and carboxylate groups on the GAG and basic residues in the protein or peptide dominate the interaction, but the thermodynamics of these electrostatic interactions have not been studied. Arginine residues occur frequently in the known heparin binding sites of proteins. Arginine is also more common than lysine in randomly synthesized 7-mer peptides that bind to immobilized heparin and heparan sulfate. We have used heparin affinity chromatography, equilibrium dialysis, and isothermal titration calorimetry techniques to further investigate these interactions. A 7-mer of arginine eluted from a heparin-affinity column at 0.82 M NaCl, whereas the analogous 7-mer of lysine eluted at 0.64 M. Similarly, the putative heparin binding site peptide (amino acid residues 110-130) from acidic fibroblast growth factor, which contained four lysine and two arginine residues, eluted at 0.50 M, whereas the analogous peptide with six lysine residues eluted at 0.41 M and one with six arginine residues eluted at 0.54 M. At 25 degrees C in 10 mM sodium phosphate, pH 7.4, carboxy and amino termini blocked arginine (blocked arginine) bound to heparin twice as tightly as blocked lysine as measured by equilibrium dialysis Similarly, at 30 degrees C in 10 mM sodium phosphate, pH 7.4, and in water, blocked arginine bound 2.5 times more tightly to anions in heparin than blocked lysine. Using titration calorimetry, the enthalpy of blocked arginine and lysine binding to heparin was 1.14 +/- 0.24 and 0.45 +/- 0.35 kJ/mol, respectively, under identical conditions. Our observations show that blocked arginine- and arginine-containing peptides bound more tightly to GAGs than the analogous lysine species and suggest that the difference was due to the intrinsic properties of the arginine and lysine side chains. The greater affinity of the guanidino cation for sulfate in GAGs is probably due to stronger hydrogen bonding and a more exothermic electrostatic interaction. This can be rationalized by soft acid, soft base concepts.
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PMID:Differences in the interaction of heparin with arginine and lysine and the importance of these basic amino acids in the binding of heparin to acidic fibroblast growth factor. 748 89

Transport of lysine by microvillous membranes was investigated by characterization of L-[3H]lysine uptake in membrane vesicles isolated from human placentas. At least one Na(+)-independent system was observed at 22 degrees C and two systems at 37 degrees C. Lysine concentration dependence data were fit by a one- or two-system model with a Michaelis-Menten constant (Km) of 124 +/- 28 microM and a maximum velocity (Vmax) of 33.1 +/- 7.7 pmol.mg protein-1.min-1 at 22 degrees C and with Km values of 1 +/- 0.6 and 245 +/- 51 microM and Vmax values of 0.14 +/- 0.07 and 45.8 +/- 8.7 pmol.mg protein-1.30 s-1 at 37 degrees C. In the presence of N-ethylmaleimide, the uptake (37 degrees C) data were fit by a one-system model with kinetic parameters similar to the lower Km system. Uptake of L-lysine in the absence of Na+ was inhibited completely by L-arginine, L-histidine, and L-homoarginine. In the presence of Na+, uptake was inhibited completely by these same three amino acids and L-leucine but only partially by other neutral amino acids. To compare directly microvillous and basal membrane from the same placenta, we examined the inhibition of 20 microM lysine uptake in the presence of Na+. Inhibition by L-leucine was similar in the two membranes. However, L-homoserine, L-alanine, and L-phenylalanine over a wide concentration range inhibited substantially less in microvillous (at both temperatures) than in basal membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lysine uptake by human placental microvillous membrane: comparison of system y+ with basal membrane. 753 87

The complete amino acid sequence of a low molecular weight peptide from the hemolymph of the housefly Musca domestica L., which had been determined to competitively inhibit phenol oxidase (PO; monophenol, dihydroxy-phenylalanine:oxygen oxidoreductase; EC 1.14.18.1) in the nM range, was unambiguously established by employing both automatic Edman degradation and mass spectrometry. The physiologically active peptide, which was designated phenol oxidase inhibitor (POI), has an observed molecular weight of 4213.1 +/- 0.2 by electrospray ionization mass spectrometry. The relatively short and structurally dense peptide contained 38 amino acid residues rich in cysteine and lysine. Comparison of the observed and calculated molecular mass indicates that apparently all six cysteine residues form disulfide bridges. Interestingly, sequence analyses of both the intact and protease-digested S-pyridylethylated POI showed that one of the two tyrosine residues (Tyr-32) is hydroxylated to a 3,4-dihydroxyphenylalanine (dopa) residue. This agreed with the increase of 16 mass units observed in mass spectrometric measurements. This was further verified by submission of free L-dopa to the sequencer, which gave a retention time consistent with the atypical peak observed at the Edman cycle of the peptide containing dopa. This study demonstrates the existence of a biologically active, dopa-containing peptide among the insects. Since the POI activity was most prominent in aged pupae, especially pharate adults, the POI may play an important role in smoothing the way of adult emergence through hindering excessive melanization, as well as hardening, of cuticular proteins under the epicuticle.
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PMID:Primary structure of a potent endogenous dopa-containing inhibitor of phenol oxidase from Musca domestica. 770 56

Lysyl hydroxylase (EC 1.14.11.4) catalyzes the formation of hydroxylysine in collagens by the hydroxylation of lysine residues in peptide linkages. This enzyme activity is known to be reduced in patients with the type VI variant of the Ehlers-Danlos syndrome, and the first mutations in the lysyl hydroxylase gene (PLOD) have recently been identified. We have now isolated genomic clones for human lysyl hydroxylase and determined the complete structure of the gene, which contains 19 exons and a 5' flanking region with characteristics shared by housekeeping genes. The constitutive expression of the gene in different tissues further suggests that lysyl hydroxylase has an essential function. We have sequenced the introns of the gene in the region where many mutations and rearrangements analyzed to date are concentrated. Intron 9 and intron 16 show extensive homology resulting from the many Alu sequences found in these introns. Intron 9 contains five and intron 16 eight Alu sequences. The high homology and many short identical or complementary sequences in these introns generate many potential recombination sites with the gene. The delineation of the structure of the lysyl hydroxylase gene contributes significantly to our understanding of the rearrangements in the genome of Ehlers-Danlos type VI patients.
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PMID:Structure and expression of the human lysyl hydroxylase gene (PLOD): introns 9 and 16 contain Alu sequences at the sites of recombination in Ehlers-Danlos syndrome type VI patients. 771 97

It was previously proposed that the activation of rat liver phenylalanine hydroxylase (EC 1.14.16.1) by cAMP-dependent protein kinase-mediated phosphorylation of Ser-16 is due to the introduction of the negatively charged phosphate group. To explore the validity of this proposal, we have applied site-directed mutagenesis to specifically replace Ser-16 with negatively charged amino acids, glutamic and aspartic; with polar uncharged amino acids, asparagine and glutamine; with the positively charged amino acid lysine; and with the nonpolar hydrophobic amino acid alanine. The wild-type and mutant enzymes were purified to homogeneity, and the importance of Ser-16 in the activation of phenylalanine hydroxylase was examined by comparing the state of activation of the phosphorylated form of the wild-type hydroxylase with that of the mutants. The kinetic studies carried out on the wild-type phosphorylated hydroxylase showed that all the activation could be accounted for by an increase in Vmax with no change in Km for either phenylalanine or the pterin cofactor. Replacement of Ser-16 with a negatively charged residue, glutamate of aspartate, resulted in the activation of the hydroxylase by 2- to 4-fold, whereas replacement with glutamine, asparagine, lysine, or alanine resulted in a much more modest increase. Further, lysolecithin was found to stimulate the phosphorylated hydroxylase and the mutant enzymes S16E and S16D by a factor of 6-7. In contrast, the mutants S16Q, S16N, and S16A all showed the same magnitude of activation as the wild-type with lysolecithin. Therefore, this study demonstrates that activation of the enzyme by phosphorylation of Ser-16 by cAMP-dependent protein kinase is due to the introduction of negative charge(s) and strongly suggests the involvement of electrostatic interaction between the regulatory and catalytic domains of the hydroxylase.
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PMID:Further studies of the role of Ser-16 in the regulation of the activity of phenylalanine hydroxylase. 776 94

Aminoacylase I (EC 3.5.1.14) encapsulated in calcium alginate beads stabilized with poly-L-lysine was used for the production of L-phenylalanine by the hydrolysis of a racemic mixture of N-acetyl-DL-phenylalanine. The immobilized aminoacylase was studied with respect to operational stability, thermal stability, effects of pH and temperature and kinetic constants. The leakage of enzyme from the stabilized beads was eliminated. The immobilized enzyme retained high biological activity. The Km and Vmax values for the stabilized beads were 11.11 mmol dm-3 and 0.076 mumol min-1 respectively. The optimum pH and temperature for the hydrolysis were 6.5 and 55 degrees C respectively. Scanning electron micrographs revealed crosslinked structures on the surface of the beads. The operational performances of the beads in a batch reaction and a packed-bed bioreactor for continuous reaction were investigated. With batch reaction, only about 5% of enzyme activity was lost within ten reaction cycles and there was no significant loss of activity over 600 h of continuous operation after equilibrium was reached, and a conversion yield of about 80% was obtained.
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PMID:Immobilization of aminoacylase by encapsulation in poly-L-lysine-stabilized calcium alginate beads. 776 83

Infusion of cobaltous-lysine into the optic nerve of juvenile Florida garfish reveals that the preoptic area, pretectum, thalamus and the mediorostral and ventrolateral poles of the optic tectum each receive bilateral, monosynaptic input. The bilateral input to the mediorostral pole of the tectum projects via the dorsal optic tract and terminates in the rostral half of the tectum. The bilateral input to the ventrolateral tectum projects via the ventral optic tract and extends the whole length of the tectum. The incidence of direct ipsilateral input to the tectum suggests binocular vision may play a functional role in the survival of this species. In order to test this hypothesis, we examined the retinal distribution of ipsilateral retinal ganglion cells that project to the mediorostral tectum and the size and location of the binocular visual field. Cell distribution was examined by retrograde labelling with rhodamine-conjugated dextran amine delivered by microinjections into the mediorostral pole of the right optic tectum. In the ipsilateral retina, ganglion cells are distributed in a narrow temporoventral area with a mean of 0.44 +/- 0.14 x 10(3) cells per mm2 apposing the retinal margin. In the contralateral retina, ganglion cells are also distributed within this temporoventral region with a mean peak density of 2.33 +/- 0.47 x 10(3) cells per mm2. Three broad classes of ipsilaterally projecting retinal ganglion cells (orthotopic cells within the ganglion cell layer, displaced cells within the inner nuclear layer, and giant cells within the ganglion and inner nuclear layers) are identified, intermingled in both the ipsilateral and contralateral retinae after retrograde labelling from the mediorostral pole of the tectum. Ophthalmoscopic mapping of the monocular and binocular visual fields reveals two small frontal wedges of binocular overlap. A dorsal wedge (12 degrees wide) extends from approximately 7 degrees above the horizontal axis to 10 degrees beyond the vertical axis, and a ventral wedge (20 degrees wide) extends approximately 10 degrees below the horizontal axis to 15 degrees beyond the vertical axis. The dorsal binocular visual field is subtended by the temporoventral region of the retina possessing both ipsilaterally and contralaterally projecting ganglion cells which terminate in the mediorostral pole of the optic tectum. Therefore, the partial decussation of retinal ganglion cell axons at the optic chiasm brings information from corresponding regions of the binocular visual field into register in the mediorostral pole of the optic tectum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The visual system of the Florida garfish, Lepisosteus platyrhincus (Ginglymodi). IV. Bilateral projections and the binocular visual field. 786 70

The leucine zipper is a dimeric coiled-coil protein structure composed of two amphipathic alpha-helices with the hydrophobic surfaces interacting to create the dimer interface. This structure has been found to mediate the dimerization of two abundant classes of DNA binding proteins: the bZIP and bHLH-Zip proteins. Several workers have reported that amino acids in the e and g positions of the coiled coil can modulate dimerization stability and specificity. Using the bZIP protein VBP as a host molecule, we report a thermodynamic scale (delta delta G) for 27 interhelical interactions in 35 proteins between amino acids in the g and the following e positions (g<==>e') of a leucine zipper coiled coil. We have examined the four commonly occurring amino acids in the e and g positions of bZIP proteins, lysine (K), arginine (R), glutamine (Q), glutamic acid (E), as well as the only other remaining charged amino acid aspartic acid (D), and finally alanine (A) as a reference amino acid. These results indicate that E<==>R is the most stable interhelical pair, being 0.35 kcal/mol more stable than E<==>K. A thermodynamic cycle analysis shows that the E<==>R pair is 1.33 kcal/mol more stable than A<==>A with -1.14 kcal/mol of coupling energy (delta delta Gint) coming from the interaction of E with R. The E<==>K coupling energy is only -0.14 kcal/mol. E interacts with more specificity than Q. The R<==>R pair is less stable than the K<==>K by 0.24 kcal/mol. R interacts with more specificity than K. Q forms more stable pairs with the basic amino acids K and R rather than with E. Changing amino acids in the e position to A creates bZIP proteins that form tetramers.
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PMID:A thermodynamic scale for leucine zipper stability and dimerization specificity: e and g interhelical interactions. 802 70


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