| 2983222 |
Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. |
10.1038/313756a0 |
Nature |
Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes.
Abstract
- We have deduced the entire 1,370-amino-acid sequence of the human insulin receptor precursor from a single complementary DNA clone. The precursor starts with a 27-amino-acid signal sequence, followed by the receptor alpha-subunit, a precursor processing enzyme cleavage site, then the beta-subunit containing a single 23-amino-acid transmembrane sequence. There are sequence homologies to human epidermal growth factor receptor and the members of the src family of oncogene products.
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| 2985580 |
Identification of residues in the nucleotide binding site of the epidermal growth factor receptor/kinase. |
10.1016/s0021-9258(18)89002-0 |
J. Biol. Chem. |
Identification of residues in the nucleotide binding site of the epidermal growth factor receptor/kinase.
Abstract
- We have purified the epidermal growth factor receptor/kinase from A431 membrane vesicles which had been affinity labeled with the ATP analog, 5'-p-fluorosulfonylbenzoyl[8-14C]adenosine. The resulting purified, affinity labeled receptor/kinase preparation has been subjected to reduction and carboxymethylation followed by tryptic digestion. From this digest, we have isolated and sequenced the tryptic peptide containing the major site of labeling by the ATP analog. The sequence of this peptide is Ile-Pro-Val-Ala-Ile-X-Glu-Leu, where X corresponds to Lys 721 of the derived sequence of the EGF receptor/kinase.
|
| 2991899 |
Characterization and sequence of the promoter region of the human epidermal growth factor receptor gene. |
10.1073/pnas.82.15.4920 |
Proc. Natl. Acad. Sci. U.S.A. |
Characterization and sequence of the promoter region of the human epidermal growth factor receptor gene.
Abstract
- The promoter region of the epidermal growth factor (EGF) receptor has been identified by in vitro transcription using EGF receptor genomic DNA fragments as template and by primer extension and nuclease S1 mapping using EGF receptor mRNA. Six transcriptional start sites were identified. DNA sequence analysis shows that the promoter region contains neither a "TATA box" nor a "CAAT box," has an extremely high G+C content (88%), and contains five CCGCCC repeats and four (TCC)TCCTCCTCC repeats. This promoter region is situated close to or within a DNase I-hypersensitive site in A431 human epidermoid carcinoma cells, which overproduce the EGF receptor. The EGF receptor gene promoter has some resemblance to the promoter of the hydroxymethylglutaryl-CoA reductase gene and the early promoter of simian virus 40. This similarity may offer a clue to the mechanism by which the receptor gene is regulated.
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| 3004508 |
Synthesis and biological activity of a lysine-containing cyclic analog of Leu5enkephalin |
None |
Bioorg Khim |
Synthesis and biological activity of a lysine-containing cyclic analog of Leu5enkephalin
Abstract
- The cyclic analogue of Leu5enkephalin--cyclo (Lys-Tyr-Gly-Gly-Phe-Leu) and two corresponding linear hexapeptides with lysine residue attached to the N- or C-terminus of the molecule have been synthesized by classical methods of peptide chemistry. The addition of lysine residue to the N-terminus of cyclization of the molecule reduce the interaction of these analogues with both central and peripheral opiate receptors. The addition of lysine residue to the C-terminus of the molecule through the epsilon-amino group does not affect the interaction of the analogue with mu-receptors but reduces approximately tenfold its affinity for delta-receptors. All three analogues have analgesic potency similar to that of Leu5enkephalin as assayed after intracisternal administration to mice.
|
| 3005838 |
Proposals for the mu-active conformation of the enkephalin analog Tyr-cyclol(-N gamma-D-A2-bu-Gly-Phe-Leu-) |
None |
Mol Pharmacol |
Proposals for the mu-active conformation of the enkephalin analog Tyr-cyclol(-N gamma-D-A2-bu-Gly-Phe-Leu-)
Abstract
- The conformational behavior of the sterically restricted cyclic peptide Tyr-cyclo(-N gamma-D-A2-bu-Gly-Phe-Leu-), proposed recently as an enkephalin analog with high opiate activity, is examined by theoretical investigations. The method used allows the search of conformational energy minima associated with cyclic structures fitting a hypothetical opiate pharmacophore. The results obtained show that, despite the fact that many cyclic structures of low conformational energy can be found for this compound, only one of them can be retained as a conformer presenting the characteristic features of the imposed pharmacophore. This conformation is stabilized by an intramolecular H-bond between the D-A2bu-carbonyl and the Leu NH group so that a beta-turn is formed. This structure also presents a high mobility of the Tyr1 side-chain which can fit the tyramine moiety of rigid opiates with minor loss of conformational energy. A two-step binding mechanism is proposed for the interactions of this cyclic peptide with its receptor which could be an intermediate between the "zipper" model proposed for flexible linear peptides and the "lock-and-key" model adapted to rigid molecules. The selectivity of enkephalin analogs for mu and delta opioid receptors is discussed in light of the present theoretical investigations.
|
| 3006723 |
Biochemical basis of alcoholism: statements and hypotheses of present research |
10.1016/0741-8329(85)90093-x. |
Alcohol |
Biochemical basis of alcoholism: statements and hypotheses of present research
Abstract
- Experimental results and theoretical considerations on the biology of alcoholism are devoted to the following topics: genetically determined differences in metabolic tolerance; participation of the alternative alcohol metabolizing systems in chronic alcohol intake; genetically determined differences in functional tolerance of the CNS to the hypnotic effect of alcohol; cross tolerance between alcohol and centrally active drugs; dissociation of tolerance and cross tolerance from physical dependence; permanent effect of uncontrolled drinking behavior induced by alkaloid metabolites in the CNS; genetically determined alterations in the function of opiate receptors; and genetic predisposition to addiction due to innate endorphin deficiency. For the purpose of introducing the most important research teams and their main work, statements from selected publications of individual groups have been classified as to subject matter and summarized. Although the number for summary-quotations had to be restricted, the criterion for selection was the relevance to the etiology of alcoholism rather than consequences of alcohol drinking.
|
| 3010995 |
In vitro activity profiles of cyclic and linear enkephalin pseudopeptide analogs |
10.1016/0006-291x(86)90500-0. |
Biochem Biophys Res Commun |
In vitro activity profiles of cyclic and linear enkephalin pseudopeptide analogs
Abstract
- The peptide bond in the 4-5 position of the cyclic and linear enkephalin analogs H-Tyr-cyclo-D-Lys-Gly-Phe-L(or D)-Leu- and H-Tyr-D-Ala-Gly-Phe-L(or D)-Leu-OH was replaced by a thiomethylene ether linkage. Each of the configurational isomers of the cyclic pseudopeptide H-Tyr-cyclo-D-Lys-Gly-Phe psi CH2SL(or D)-Leu- showed high potency in both the guinea pig ileum and the mouse vas deferens assay and, therefore, had no preference for either mu- or delta-opioid receptors, in contrast to the cyclic parent peptides H-Tyr-cyclo-D-Lys-Gly-Phe-L(or D)-Leu- which are mu-receptor selective. The loss of selectivity observed with the cyclic pseudopeptides may be due to the greater flexibility of their 18-membered ring structures as a consequence of the peptide bond substitution. The linear pseudopeptide analogs were both less potent and less delta-receptor selective than their parent compounds. These results indicate that thiomethylene ether peptide bond replacements can have a pronounced effect on the activity profile of peptide hormones and neurotransmitters.
|
| 3011602 |
Cloning, characterization and nucleotide sequences of two cDNAs encoding human pancreatic trypsinogens |
10.1016/0378-1119(86)90111-3. |
Gene |
Cloning, characterization and nucleotide sequences of two cDNAs encoding human pancreatic trypsinogens
Abstract
- Two cDNA clones encoding two major human trypsinogen isozymes were isolated from a human pancreatic cDNA library. The deduced amino acid (aa) sequences of the two trypsinogen precursors are found to have 89% sequence homology, and have the same number of aa (247), including 15 aa for a signal peptide and 8 aa for an activation peptide. Southern blot analysis of human genomic DNA using the cloned cDNA as a probe, revealed that the human trypsinogen genes constitute a multigene family of more than ten genes.
|
| 3014910 |
Neurohypophysial peptide potencies in cultured anuran epithelia (A6) |
10.1152/ajpregu.1986.251.1.R77. |
Am J Physiol |
Neurohypophysial peptide potencies in cultured anuran epithelia (A6)
Abstract
- To characterize the V2 receptor (for antidiuretic hormone), we have studied the effect of a number of neurohypophysial hormone analogues on cyclic AMP (cAMP) accumulation and short-circuit current in cultured epithelia formed by A6 cells. A6 is the designation of a continuous cell line derived from the kidney of Xenopus laevis. The order of potency for stimulating cAMP accumulation and short-circuit current in A6 epithelia is like that for stimulating water permeability in toad urinary bladder. As anticipated, arginine vasotocin (AVT), the antidiuretic hormone of Amphibia, is more potent than arginine vasopressin (AVP), the antidiuretic hormone of most mammals. The two hormones differ only in the third amino acid (Phe-3 in AVP is a substitution for Ile-3 in AVT). However, there are a number of striking differences in the responsiveness of these amphibian V2 receptors and mammalian V2 receptors to changes in the 7th, 8th, and 9th amino acids where AVT and AVP are identical. 1) Substitution of Lys-8 for Arg-8 in AVP results in marked loss of potency in Amphibia, whereas there is only modest loss of potency in mammals. 2) Desglycinamide AVP is nearly as potent as AVP in Amphibia, whereas it is inactive in mammals. 2) Tocinoic acid, lacking amino acids 7, 8, and 9, has activity in Amphibia, but pressinoic acid, lacking the same three amino acids, is inactive.
|
| 3024560 |
In vitro and in vivo activity of LY 146032, a new cyclic lipopeptide antibiotic |
10.1128/AAC.30.4.532. |
Antimicrob Agents Chemother |
In vitro and in vivo activity of LY 146032, a new cyclic lipopeptide antibiotic
Abstract
- The in vitro activity of LY 146032, a cyclic lipopeptide antibiotic belonging to the class of agents designated A21978C, was compared with those of vancomycin, cefpirome, cefotaxime, and clindamycin against selected gram-positive bacteria. The new drug inhibited all staphylococcal isolates, including methicillin-resistant strains, at concentrations of less than or equal to 1.0 microgram/ml. The activity of LY 146032 was comparable to that of vancomycin against most streptococci, but the latter demonstrated greater potency against Streptococcus faecium and penicillin-resistant strains of pneumococci and viridans group streptococci. LY 146032 was markedly less active than vancomycin against Listeria monocytogenes (MICs for 90% of strains tested, 16 and 1.0 microgram/ml, respectively). The activity of LY 146032 was enhanced as the concentration of calcium in the test medium was increased. MBCs were within eightfold of the MIC for each of 12 strains tested. In a rat model of enterococcal endocarditis, the administration of LY 146032 resulted in increased survival and a reduction in the bacterial titer within cardiac vegetations compared with untreated control animals.
|
| 3032093 |
Decreased binding of antibiotics to lipopolysaccharides from polymyxin-resistant strains of Escherichia coli and Salmonella typhimurium |
10.1128/AAC.31.2.230. |
Antimicrob Agents Chemother |
Decreased binding of antibiotics to lipopolysaccharides from polymyxin-resistant strains of Escherichia coli and Salmonella typhimurium
Abstract
- The interactions of polycationic antibiotics with lipopolysaccharide (LPS) isolated from parental and polymyxin-resistant strains of Salmonella typhimurium and Escherichia coli were measured by using a cationic spin probe. Electron spin resonance spectra indicated that increasing concentrations of cations competitively displaced probe from LPS aggregates. Polymyxin B and other cations displaced less probe from LPS of polymyxin-resistant strains than from LPS of the parental strains, whereas the same amount or more probe was displaced from isolates of the mutants by the structurally similar antibiotic, EM 49 (octapeptin). In general, the differential affinities of these antibiotics for LPS correlated with their antibiotic activity in vivo, suggesting that resistance results from a decrease in antibiotic permeability across the outer membrane due to alterations in the LPS which affect antibiotic binding. The alterations in the structure of LPS from the polymyxin-resistant mutants of E. coli were characterized using 31P nuclear magnetic resonance spectroscopy. The results suggested that esterification of the core-lipid A phosphates is responsible for increased resistance to polymyxin B and that this alteration is different from that previously proposed for the S. typhimurium strains. In both cases, however, resistance was the result of modifications that result in a less acidic lipid A.
|
| 3033220 |
Effects of oxytocin-related peptides on acute morphine tolerance: opposite actions by oxytocin and its receptor antagonists |
None |
J Pharmacol Exp Ther |
Effects of oxytocin-related peptides on acute morphine tolerance: opposite actions by oxytocin and its receptor antagonists
Abstract
- The hormonally and behaviorally active nonapeptide oxytocin (OXT), its behaviorally active N-terminal octapeptide desglycinamide9-OXT and Z-prolyl-D-leucine, a synthetic analog of the C-terminal prolyl7-leucine8 sequence, inhibited the development both of a moderate and of a strong tolerance to morphine. N-alpha-Acetyl-(2-0-methyltyrosine)-OXT and (penicillamine1-2-0-methyltyrosine)- lysine8-vasopressin, both OXT receptor antagonists, facilitated the development of a moderate morphine tolerance. The i.c.v. injection of either antagonist prevented the effects of i.c.v. and s.c. OXT treatment on the development of tolerance. The effect of desglycinamide9-OXT, but not that of Z-prolyl-D-leucine was also prevented by N-alpha-acetyl-(2-0-methyltyrosine)-OXT. It is concluded that OXT and desglycinamide9-OXT, but not Z-prolyl-D-leucine, attenuate morphine tolerance by affecting putative oxytocinergic binding sites in the mouse brain. The fact that i.c.v. injection of the receptor antagonist also blocked the effect of s.c. OXT treatment argues in favor of the possibility that a minor proportion of s.c. OXT (or behaviorally active fragments thereof) may reach central nervous system target sites.
|
| 3037284 |
The role of ribosomes in the sensitivity of mycobacteria to tuberactinomycin |
10.1111/j.1348-0421.1987.tb03081.x. |
Microbiol Immunol |
The role of ribosomes in the sensitivity of mycobacteria to tuberactinomycin
Abstract
|
| 3039909 |
Receptors for epidermal growth factor and other polypeptide mitogens. |
10.1146/annurev.bi.56.070187.004313 |
Annu. Rev. Biochem. |
Receptors for epidermal growth factor and other polypeptide mitogens.
Abstract
|
| 3045093 |
Increased cell surface hydrophobicity of a Serratia marcescens NS 38 mutant lacking wetting activity |
10.1128/jb.170.9.4361-4364.1988. |
J Bacteriol |
Increased cell surface hydrophobicity of a Serratia marcescens NS 38 mutant lacking wetting activity
Abstract
- The cell surface hydrophobicity of Serratia marcescens appears to be an important factor in its adhesion to and colonization of various interfaces. The cell surface components responsible for mediating the hydrophobicity of S. marcescens have not been completely elucidated, but may include prodigiosin and other factors. In the present report we have investigated the potential role of serratamolide, an amphipathic aminolipid present on the surfaces of certain S. marcescens strains, in modulating cell surface hydrophobicity. The hydrophobic properties of a serratamolide-producing strain (NS 38) were compared with those of a serratamolide-deficient mutant (NS 38-9) by monitoring the kinetics of adhesion to hexadecane. Serratamolide production was monitored by thin-layer chromatography and the wetting activity of washed-cell suspensions on polystyrene. Wild-type NS 38 cells were far less hydrophobic than the serratamolide-deficient mutant cells were; the removal coefficients were 48 min-1 for the mutant, as compared with only 18 min-1 for the wild type. The data suggest that the presence of serratamolide on S. marcescens cells results in a reduction in hydrophobicity, presumably by blocking hydrophobic sites on the cell surface.
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