| 6258151 |
The translocation inhibitor tuberactinomycin binds to nucleic acids and blocks the in vitro assembly of 50S subunits |
10.1093/nar/8.23.5767. |
Nucleic Acids Res |
The translocation inhibitor tuberactinomycin binds to nucleic acids and blocks the in vitro assembly of 50S subunits
Abstract
- Binding studies were performed with a 14C-labelled derivative of viomycin, tuberactinomycin 0 (TUM O). TUM O bound to 30S and 50S subunits. The binding component was the RNA, since ribosomal proteins did not bind the drug. Other RNAs such as tRNA, phage RNA (MS2), and homopolynucleotides also bound the drug. Striking differences in the binding capacity of the various homopolynucleotides were found. Poly(U) bound strongly, poly(G) and poly(C) bound intermediately, whereas poly(A) showed a very low binding. DNA also bound TUM O, although with native DNA the binding was only weak. Finally the effects of viomycin on the assembly in vitro of the 50S subunit from E. coli were tested. A very strong inhibition was found: when the reconstitution was performed at 0.5 x 10(-6) M viomycin the particles formed sedimented at about 50S, but showed a residual activity of less than 10%. The inhibitory power of viomycin with respect to the in vitro assembly is more pronounced than that found in in vitro systems for protein synthesis.
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| 6261242 |
A cyclic enkephalin analog with high in vitro opiate activity |
10.1073/pnas.77.12.7162. |
Proc Natl Acad Sci U S A |
A cyclic enkephalin analog with high in vitro opiate activity
Abstract
- A conformationally restricted analog of Leu5enkephalin was synthesized by cyclization of the COOH-terminal carboxyl group of leucine to the gamma-amino moiety of alpha, gamma-diaminobutyric acid (A2bu) substituted in position 2 of the peptide. Relative to Leu5enkephalin, the cyclic analog with D configuration in position 2, H-Tyr-cyclo(-N gamma-D-A2bu-Gly-Phe-Leu-), was 17.5 times more potent in the guinea pig ileum assay and twice as potent in the rat brain receptor binding assay, whereas its diastereomer H-Tyr-cyclo(-N gamma-L-A2bu-Gly-Phe-Leu-) showed low activity. The cyclic D isomer was also slightly more active than the open-chain reference compound D-Nva2, Leu5enkephalinamide in both assays, and it proved to be highly resistant to degradation by brain "enkephalinases." The steric constraints introduced in H-Tyr-cyclo(-N gamma-D-A2bu-Gly-Phe-Leu-) were shown to prevent the realization of most of the conformational features ascribed to linear enkephalin in solution or in the crystalline state and permitted an assessment of proposed models of the conformation of enkephalin when it is bound to the receptor.
|
| 6261739 |
Behavioral activity of met-enkephalin and ACTH4-10 and other peptides containing a phenylalanine and methionine residue |
10.1016/0006-291x(81)90857-3. |
Biochem Biophys Res Commun |
Behavioral activity of met-enkephalin and ACTH4-10 and other peptides containing a phenylalanine and methionine residue
Abstract
|
| 6273089 |
Actinomycin D derivatives that recognize 2 DNA GC pairs: bis-actinomycin D |
None |
Dokl Akad Nauk SSSR |
Actinomycin D derivatives that recognize 2 DNA GC pairs: bis-actinomycin D
Abstract
|
| 6273344 |
Conformation of cyclo-(L-threonine)2 and cyclo-(L-allothreonine)2. A proton and carbon n.m.r study |
None |
Int J Pept Protein Res |
Conformation of cyclo-(L-threonine)2 and cyclo-(L-allothreonine)2. A proton and carbon n.m.r study
Abstract
- The diketopiperazines cyclo-(L-Thr)2 and cyclo-(L-allo Thr)2 in water and in dimethyl sulfoxide were studied by proton and carbon-13 nuclear magnetic resonance, and the dominant conformation were deduced from proton-proton and proton-carbon coupling constants. In cyclo-(L-Thr)2 the chi 1 = 60 degrees, hydroxyl over the ring, side chain conformation is favored; this conformation is also favored for cyclo-(L-Ser)2 and cyclo-(L-Ser-D-Ser). However, the important side chain conformation for cyclo-(L-allo Thr)2 is chi 1 = -60 degrees, methyl group over the diketopiperazine ring. The determining factors are apparently steric. The diketopiperazine ring of cyclo-(L-Thr)2 is puckered to hold the side chains more nearly axial than is that of cyclo-(L-allo Thr)2. although the degree of ring folding is probably not large.
|
| 6305407 |
Characterization of the complementary deoxyribonucleic acid and gene coding for human prothrombin. |
10.1021/bi00278a008 |
Biochemistry |
Characterization of the complementary deoxyribonucleic acid and gene coding for human prothrombin.
Abstract
- The DNA sequences of a complementary deoxyribonucleic acid (cDNA) and a portion of the gene coding for human prothrombin have been determined. The cDNA was 2005 base pairs in length and was found to code for part of a leader sequence of 36 amino acids, 579 amino acids present in the mature protein, a stop codon, a noncoding region of 97 base pairs, and a poly(A) tail of 27 base pairs. It is proposed that the leader sequence consists of a signal sequence and a pro sequence for the mature protein that circulates in plasma. The 10 glutamic acid residues that are present in the amino-terminal region of prothrombin and are converted to gamma-carboxyglutamic acid in the mature protein are coded by only the GAG codon. The cDNA for prothrombin was also employed as a probe for screening a human fetal liver genomic DNA library. One of the strongly positive phage containing a human DNA insert of 5 kilobases was mapped with restriction endonucleases and sequenced. This DNA contained approximately half of the gene for human prothrombin and included six introns and five exons coding for amino acid residues 144-448. The two largest intervening sequences in the genomic DNA contained two copies each of AluI repetitive DNA.
|
| 6310598 |
Bis-penicillamine enkephalins possess highly improved specificity toward delta opioid receptors |
10.1073/pnas.80.19.5871. |
Proc Natl Acad Sci U S A |
Bis-penicillamine enkephalins possess highly improved specificity toward delta opioid receptors
Abstract
- The conformationally restricted, cyclic, disulfide-containing, enkephalin analogs 2-D-penicillamine, 5-L-penicillamineenkephalin (D-Pen2,L-Pen5enkephalin) and 2-D-penicillamine, 5-D-penicillamineenkephalin (D-Pen2,D-Pen5enkephalin) were synthesized by solid-phase methods. Selectivities of these analogs for a single class of opioid receptor were investigated by examining relative potencies in the mouse vas deferens assay, in which the functional receptor is the delta receptor, versus the guinea pig ileum assay, in which the mu receptor is the functional receptor, and by determining their relative abilities to displace the prototypical delta receptor ligand D-Ala2, D-Leu5enkephalin and the prototypical mu receptor ligand naloxone from rat brain membrane preparations. Based on these comparisons D-Pen2,L-Pen5- and D-Pen2,D-Pen5enkephalin exhibited delta receptor selectivities of 1,088 and 3,164, respectively, in the bioassays, and 371 and 175, respectively, in the binding assays. Compared with the previously reported delta receptor selective analogs, D-Ala2,D-Leu5enkephalin, D-Ser2,Leu5,Thr6enkephalin, and D-Thr2,Leu5,Thr6enkephalin, the bis-Pen-containing analogs provide an order of magnitude increase in delta receptor selectivity.
|
| 6315109 |
Mechanism of action of cyclokinins |
None |
Biull Eksp Biol Med |
Mechanism of action of cyclokinins
Abstract
- Cyclic analogs of bradykinin (CBK) and kallidin (CK) have a weak myotropic activity and a marked and prolonged hypotensive effect unlike linear bradykinin (BK) and kallidin (K) which produce a short-term hypotension and considerable contraction of rat uterus smooth muscles. Myotropic effects of BK and CK were significantly inhibited by phentolamine, methysergide, papaverine and verapamil. Atropine, diphenhydramine and propranolol have no influence on the kinin-induced myotropic responses. The prolonged decrease in blood pressure induced by CBK and CK is observed in un- and anesthetized normotensive, spontaneously hypertensive rats and rats with renovascular hypertension and is absent from anesthetized cats and guinea-pigs. This indicates the species specificity of cyclokinins. Indomethacin, diphenhydramine and methysergide failed to influence the BK- and CK-induced hypotensive effects on anesthetized rats. CaCl2 did not influence the magnitude of the hypotensive effect of BK and CK, however, it significantly shortened the duration of the CK-induced hypotensive effect. In vitro CBK and CK inhibited activity of kininase II in a similar manner (at a concentration range of 10(-5) M) but to a less extent than BK (10(-7)-10(-6) M). It is suggested that the hypotensive effect of CK is mediated at least partly via Ca2+-dependent systems and inhibition of kininase II.
|
| 6315666 |
Isolation and characterization of ancovenin, a new inhibitor of angiotensin I converting enzyme, produced by actinomycetes |
10.7164/antibiotics.36.1295. |
J Antibiot (Tokyo) |
Isolation and characterization of ancovenin, a new inhibitor of angiotensin I converting enzyme, produced by actinomycetes
Abstract
- Ancovenin, an inhibitor of angiotensin I converting enzyme isolated from the culture broth of a Streptomyces species, is a dialysable peptide composed of sixteen amino acid residues containing unusual amino acids such as threo-beta-methyllanthionine, meso-lanthionine, and dehydroalanine.
|
| 6319901 |
Cyclic penicillamine containing enkephalin analogs display profound delta receptor selectivities |
10.1016/0024-3205(83)90538-6. |
Life Sci |
Cyclic penicillamine containing enkephalin analogs display profound delta receptor selectivities
Abstract
- The cyclic, penicillamine(beta, beta dimethylcysteine)-containing enkephalin analogs, D-Cys2, L-Pen5-and D-Cys2, D-Pen5enkephalin and the corresponding bis-penicillamine analogs, D-Pen2, L-Pen5-and D-Pen2, D-Pen5enkephalin were synthesized and evaluated for opioid activity in the guinea pig ileum (GPI) and mouse vas deferens (MVD) bioassays and in rat brain and neuroblastoma-glioma cell membrane binding assays. These analogs all displayed delta receptor selectivity as assessed by IC50(GPI)/IC50(MVD) ratios and by their relative potencies for displacing 3Hnaloxone (NAL) vs. 3H D-Ala2, D-Leu5enkephalin (DADLE) from rat brain membrane preparations. For D-Pen2, L-Pen5- and D-Pen2, D-Pen5enkephalin the observed IC50(GPI)/IC50 (MVD) ratios (1088 and 3164) and IC50NAL/IC50DADLE ratios (371 and 175) represent a vast improvement over previously reported delta receptor selective ligands.
|
| 6323392 |
Mechanism of inhibition of activated protein C by protein C inhibitor. |
10.1093/oxfordjournals.jbchem.a134583 |
J. Biochem. |
Mechanism of inhibition of activated protein C by protein C inhibitor.
Abstract
- Protein C inhibitor isolated from human plasma inhibited thrombin, factor Xa, trypsin and chymotrypsin as well as activated protein C, but had very little effect on urokinase and plasmin. The inhibition constants (K1) of protein C inhibitor for activated protein C, thrombin and factor Xa were 5.6 X 10(-8) M, 6.7 X 10(-8) M and 3.1 X 10(-7) M, respectively. The second-order rate constant for inhibition of activated protein C by the inhibitor increased about 30-fold in the presence of an optimal heparin concentration (5-10 units/ml). The inhibition of activated protein C by plasma protein C inhibitor was also accelerated by heparin. When activated protein C (Mr = 62,000) was incubated with protein C inhibitor (Mr = 57,000), enzyme-inhibitor complexes with apparent Mr = 102,000 and 88,000 were observed in the nonreduced and the reduced samples, respectively, on SDS-polyacrylamide gel electrophoresis. In addition to these complexes, a band of unbound enzyme and a band with Mr = 54,000 were detected. When 125I-labeled protein C inhibitor was exposed to activated protein C, the inhibitor band was converted to bands with apparent Mr = 102,000 and 54,000 in the nonreduced samples, as determined by autoradiography after gel electrophoresis in SDS. The band with Mr = 54,000 also appeared when the inhibitor reacted with other serine proteases. The activated protein C was released from the inactive complex by treatment with 1 M ammonia or hydroxylamine. This phenomenon was found by SDS-polyacrylamide gel electrophoresis to represent the dissociation of the enzyme-inhibitor complex by ammonia or hydroxylamine into the free enzyme and the proteolytically modified inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
|
| 6324343 |
Production of an epidermal growth factor receptor-related protein. |
10.1126/science.6324343 |
Science |
Production of an epidermal growth factor receptor-related protein.
Abstract
- Human epidermoid carcinoma A431 cells in culture produce a soluble 105-kilodalton protein which, by the criteria of epidermal growth factor (EGF) binding, recognition by monoclonal and polyclonal antibodies to the EGF receptor, amino-terminal sequence analysis and carbohydrate content, is related to the cell surface domain of the EGF receptor. The high rate of production and the finding that with biosynthetic labeling the specific activity of this 105-kilodalton protein exceeds that of the intact receptor indicate that it is not derived from membrane-bound mature receptor but is separately produced by the cell. These cells thus separately synthesize an EGF receptor that is inserted into the membrane and an EGF receptor-related protein that is secreted.
|
| 6325948 |
ATP-stimulated interaction between epidermal growth factor receptor and supercoiled DNA. |
10.1038/309270a0 |
Nature |
ATP-stimulated interaction between epidermal growth factor receptor and supercoiled DNA.
Abstract
- The receptor for epidermal growth factor (EGF) has been identified as a transmembrane glycoprotein that has tyrosine-specific kinase activity. The kinase activity of the receptor is enhanced in the presence of EGF (or related peptides), and the phosphorylation of a number of substrates, as well as autophosphorylation of the receptor, has been reported. Analogous findings have been described for the insulin receptor and the receptor for platelet-derived growth factor (PDGF). Thus, a number of hormone receptors and several viral transforming proteins appear to share the highly unusual property of tyrosine-specific kinase activity. Nevertheless, the specific relationship between tyrosine kinase activity and the control of cell growth and replication is unknown. It is known that after the initial binding of EGF to the plasma membrane, the hormone together with its receptor is rapidly internalized in endocytic vesicles and the hormone is eventually degraded in lysosomes. It is possible that the function of EGF is simply to stimulate internalization of its receptor, and that as a result of its altered location the receptor is able to phosphorylate a cytoplasmic component or even interact directly with a nuclear component. We now report that the purified receptor for EGF is able to interact with and nick supercoiled double-stranded DNA in an ATP-stimulated manner.
|
| 6326261 |
Expression cloning of human EGF receptor complementary DNA: gene amplification and three related messenger RNA products in A431 cells. |
10.1126/science.6326261 |
Science |
Expression cloning of human EGF receptor complementary DNA: gene amplification and three related messenger RNA products in A431 cells.
Abstract
- In order to further define the mechanisms by which polypeptide growth factors regulate gene transcription and cellular growth, expression cloning techniques were used to select human epidermal growth factor (EGF) receptor complementary DNA clones. The EGF 3' coding domain shows striking homology to the transforming gene product of avian erythroblastosis virus (v-erbB). Over-expression of EGF receptors in A431 cell lines correlates with increased EGF receptor mRNA levels and amplification (up to 110 times) of the apparently singular EGF receptor gene. There appear to be three cytoplasmic polyadenylated RNA products of EGF receptor gene expression in A431 cells, one of which contains only 5' (EGF binding domain) sequences and is postulated to encode the secreted EGF receptor-related protein.
|
| 6328312 |
Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. |
10.1038/309418a0 |
Nature |
Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells.
Abstract
- The complete 1,210-amino acid sequence of the human epidermal growth factor (EGF) receptor precursor, deduced from cDNA clones derived from placental and A431 carcinoma cells, reveals close similarity between the entire predicted v-erb-B mRNA oncogene product and the receptor transmembrane and cytoplasmic domains. A single transmembrane region of 23 amino acids separates the extracellular EGF binding and cytoplasmic domains. The receptor gene is amplified and apparently rearranged in A431 cells, generating a truncated 2.8-kilobase mRNA which encodes only the extracellular EGF binding domain.
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