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1. |
Cyclic hexapeptides related to somatostatin Synthesis and biological testing |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 5,
1990,
Page 401-417
CHRISTIAN PATTARONI,
PIERLUIGI LUCIETTO,
MURRAY GOODMAN,
GAIL YAMAMOTO,
WYLIE VALE,
LUIS MORODER,
LUCIA GAZERRO,
WALTER GÖHRING,
BERNHARD SCHMIED,
ERICH WÜNSCH,
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摘要:
As a continuation of our program to study the structure‐function relationship of the peptide hormone somatostatin, we report the synthesis and biological potencies of a series of cyclic hexapeptide analogs related to somatostatin. The parent peptide of this series was designed by Veber and coworkers, c[‐Pro6‐Phe7‐d‐Trp8‐Lys9‐Thr10‐Phe11‐], and has been reported to be superactive in the inhibition of the release of growth hormone. (The superscript numbers refer to the positions of residues in native somatostatin.) The series of analogs has been designed to examine the role of the so‐called bridging region, Phe11‐Pro6, which has been postulated to be important in maintaining the proper conformation of the biologically active tetrapeptide, Phe‐d‐Trp‐Lys‐Thr. We have incorporated peptidomimetics and the retro‐inverso modification into the bridging region of the molecule, with the aim of affecting the conformational preferences found in the parent peptide. Results from the biological assay—in vitroinhibition of growth hormone—and the conformational analysis (adjoining paper) of our analogs will provide insight into the relationship between structure and
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb01300.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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2. |
Cyclic hexapeptides related to somatostatin Conformational analysis employing1H‐NMR and molecular dynamics |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 5,
1990,
Page 418-432
DALE F. MIERKE,
CHRISTIAN PATTARONI,
NANCY DELAET,
ANNA TOY,
MURRAY GOODMAN,
TEODORICO TANCREDI,
ANDREA MOTTA,
PIERO A. TEMUSSI,
LUIS MORODER,
GUNTER BOVERMANN,
ERICH WÜNSCH,
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摘要:
We report the conformational analysis of a series of cyclic hexapeptides related to the hormone somatostatin utilizing1H NMR spectroscopy and NOE restrained molecular dynamics. The conformational preferences and results from biological analysis of these analogs (previous paper) allow for refinement of the current understanding of the structure‐activity relationship of somatostatin. For most of the molecules examined, a βII′ turn about thed‐tryptophan‐lysine residues, postulated to be required for biological activity, was present. From the NOE restrained molecular dynamics, it can be seen that the turn structure is important for the maintenance of the proper orientation of the side chains of the adjacent phenylalanine, tryptophan and lysine. The biologically active analogs have the side chains of lysine andd‐tryptophan extended away from the 18‐membered ring in close proximity to each other for a significant portion of the dynamic simulations. Although other conformations are accessible and monitored during the simulations, we believe this is important for biological recognition. The absence of the βII′ turn at thed‐tryptophan‐lysine disrupts this side chain array producing inactive molecules. The role of the bridging region, the Phe‐Pro dipeptide, is to stabilize the βII′ turn and help maintain the proper orientation of the biological
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb01301.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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3. |
Synthesis and properties of cholecystokinin‐releasing peptide (monitor peptide), a 61‐residue trypsin inhibitor |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 5,
1990,
Page 433-439
YAO‐ZHONG LIN,
DANIEL D. ISAAC,
JAMES P. TAM,
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摘要:
A 61‐residue cholecystokinin‐releasing peptide (monitor peptide), which was obtained from rat pancreatic juice and found to stimulate pancreatic enzyme secretion, was recently reported to inhibit bovine trypsin and to possess epidermal growth factor (EGF)‐like activities, at a concentration of about 10nM. However, monitor peptide is structurally different from the EGF family of growth factors. To investigate whether monitor peptide contains the supposed EGF‐like activities, it has been synthesized together with its [Ala23, Ala47] analog. The purified peptides, which were fully characterized by a range of methods including Cf‐252 ionization mass spectrometry and enzymatic digestion to establish the locations of disulfide linkages, were shown to belong to the pancreatic secretory trypsin inhibitor family and not to the EGF family. Neither synthetic monitor peptide nor its analog were able to compete with125I‐EGF in A‐431 cells or to stimulate growth of Swiss 3T3 and NRK 49F cells, up to 1 μM concentration. However, synthetic monitor peptide was as effective as the native product in the inhibition of trypsin. Replacement of the essential Arg23 in the [Ala23, Ala47]‐analog led to loss of trypsin inh
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb01302.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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4. |
Quantitative structure‐activity relationships for sea anemone polypeptide toxins |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 5,
1990,
Page 440-444
SVEN HELLBERG,
WILLIAM R. KEM,
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摘要:
Sea anemone polypeptides vary considerably in their affinities for sodium channels occurring in different excitable cells. The amino acid sequence variation in a set of six sea anemone type I polypeptide toxins (46–49 residues long), was parameterized using descriptor scales z1, z2, and z3, derived from a large number of amino acid physicochemical properties. The pharmacological properties of the toxins were represented by the results from four bioassays on crab, mouse, and rat brain and from rat heart. By means of the descriptor scales and the multivariate data analytical method PLS (partial least squares projections to latent structures), it was possible to develop quantitative structure‐activity relationships (QSAR). Using the QSARs derived from the set of six polypeptide toxins the pharmacological properties of two homologous sea anemone polypeptide toxins were predicted. Thus it is shown that QSARs may be formulated for relatively long bioactive polypeptides. The QSARs indicate that 11 different amino acid positions may be of importance, but that positions no. 5, 21, 28, 34, 37, and 40 were of main importance in modeling the relative toxicities of the six polypepti
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb01303.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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5. |
Complete amino acid sequence of a subunit from rapeseed high molecular weight protein |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 5,
1990,
Page 445-449
R. BHUSHAN,
V.K. MAHESH,
P.V. MALLIKHARJUN,
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摘要:
A subunit (M, 15 600) from the high molecular weight protein from rapeseed was separated and isolated; its purity and homogeneity were ascertained. The subunit was cleaved with cyanogen bromide, trypsin, chymotrypsin, andStaphylococcus aureusV8 protease. The fragments were separated and isolated by polyacrylamide gel electrophoresis, gel filtration, column chromatography on Dowex 1 × 2, and paper electrophoresis. The amino acid compositions of the intact subunit and different fragments obtained from enzymatic and chemical cleavages were determined. The subunit and its fragments were sequenced by manual Edman method. The phenylthiohydantoin amino acids obtained after each step were identified by thin‐layer chromatography and ultraviolet spectroscopy. The complete amino acid sequence of the subunit consisting of 125 amino acid residues has been established by the overlapping meth
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb01304.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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6. |
Further studies on proctolin analogues modified in position 2 of the peptide chain and their influence on heart‐beat frequency of insects |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 5,
1990,
Page 450-456
HUBERT BARTOSZ‐BECHOWSKI,
GRZEGORZ ROSIńSKI,
DANUTA KONOPIńSKA,
PREZEMYSŁAW SUJAK,
WIESLAW SOBÓTKA,
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摘要:
Seven proctolin analogues (I‐VII) modified in position 2 of the peptide chain by Phe (p‐guanidino) (I), Phe (p‐OEt) (II), Tyr (3′‐NH2) (III), Tyr (3′‐NO2) (IV), Afb (p‐OH) (V) (Afb = 3‐amino‐4‐phenyl‐l‐butyric acid), Afb (p‐NH2) (VI), Afb (p‐NO2) (VII), and the tetrapeptide Tyr (3′‐NH2)‐Leu‐Pro‐Thr (VIII) were synthesized by the classic liquid‐phase method. The biological effects of the peptides were investigated in cardioexcitatory tests on two insect species, the cockroachPeriplaneta americanaL., and the yellow mealworm,Tenebrio molitorL. Within physiological concentrations (10−9‐ 10−7M) peptides II, III, and IV stimulated the heart action ofP. americanalike proctolin itself. Under identical conditions, in the case ofT. molitor, only peptide III showed cardiostimulatory properties, whereas other compounds (including II and IV) were inactive at concentrations up to 10−7m. Results reported here reflect, with reference to the analogues I‐VII, selective recognition of receptors on myocardium of both insect species. The tetrapeptide VIII revealed a weak deaccelera
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb01305.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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7. |
Complete amino acid sequence of goose VLDV‐neurophysin Traces of a putative gene conversion between promesotocin and provasotocin genes |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 5,
1990,
Page 457-464
GILLES MICHEL,
BRIGITTE LÉVY,
MARIE‐THÉRÈSE CHAUVET,
JACQUELINE CHAUVET,
ROGER ACHER,
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摘要:
Goose VLDV‐neurophysin (mesotocin‐associated neurophysin) has been purified from posterior pituitary glands through molecular sieving on Sephadex G‐75 and high‐pressure reverse‐phase liquid chromatography on Nucleosil C‐18 columns. Despite apparent molecular mass of unreduced VLDV‐neurophysin measured by polyacrylamide gel electrophoresis with sodium dodecylsulfate appeared near 17kDa, this value fell to 11 kDa after reduction with mercaptoethanol, suggesting the existence of a homodimer. Complete amino acid sequence (93 residues) of goose VLDV‐neurophysin has been determined.N‐ andC‐terminal sequences of the protein have been established by Edman degradation (microsequencing) and use of carboxypeptidase Y, respectively. Peptides derived from oxidized or carboxamidomethylated neurophysin by trypsin or staphylococcal proteinase hydrolyses have been isolated by high‐pressure liquid chromatography and microsequenced, allowing determination of the complete sequence. Comparison within the vertebrate VLDV‐neurophysin lineage, namely goose VLDV‐neurophysin to mammalian VLDV‐neurophysins and to deduced toad VLDV‐neurophysin, reveals a residue insertion between positions 66 and 67 in the nonmammalian VLDV‐neurophysins. When goose MSEL‐neurophysin (vasotocin‐associated neurophysin) and goose VLDV‐neurophysin are compared to their bovine counterparts, identical substitutions are found in positions 17 (Asn in both goose neurophysins instead of Gly in both ox neurophysins), 18 (Arg instead of Lys), 35 (Tyr instead of Phe), and 41 (Thr instead of Ala). Identity of the sequences 10‐74 in both ox neurophysins has been explained by partial gene conversion between oxytocin and vasopressin genes, and identical substitutions in both goose neurophysins might reveal a similar gene conversion between m
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb01306.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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8. |
Effects of hydrophobic substitutions at position 18 on the potency of parathyroid hormone antagonists |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 5,
1990,
Page 465-470
MICHAEL CHOREV,
ELIAHU ROUBINI,
MARK E. GOLDMAN,
ROBERTA L. McKEE,
SUSAN W. GIBBONS,
JANE E. REAGAN,
MICHAEL P. CAULFIELD,
MICHAEL ROSENBLATT,
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摘要:
Position 18 in a parathyroid hormone (PTH) antagonist, [Nle8,18,Tyr34]bPTH(7‐34)NH2(ii), was shown to tolerate substitutions by a range of amino acids with retention of inhibitory activity. The effects of hydrophobic substitutions at this position as a means of enhancing binding interactions with the receptor were evaluated. Substitution of Nle at position 18 with eitherd‐Ala,d‐Trp, orl‐Trp in analog ii or with Trp (dorl) in the recently reported, highly potent antagonist, [Nle8,18,d‐Trp12,Tyr34]bPTH(7‐34)NH2(in vitroactivities; Kb= 15 nM and Ki= 125 nM), was performed. In terms of activity on renal receptors, one antagonist, [Nle8,d‐Trp12,18,Tyr34]bPTH(7‐34)NH2, is the most activein vitroPTH antagonist yet reported (Kb= 4nm; Ki= 30 nM). The rationale for design of this antagonist and the conclusions regarding PTH‐receptor interacti
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb01307.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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9. |
Side reaction of pyrenylalanine‐peptides containingNG‐tosylarginine during detosylation with hydrogen fluoride |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 5,
1990,
Page 471-475
HIROSHI NAKAMURA,
SANNAMU LEE,
SHIN ONO,
TAMAKI KATO,
HARUHIKO AOYAGI,
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摘要:
Formation of by‐products of pyrenylalanine‐peptides was observed during the cleavage of a tosyl group in pyrenylalanine‐peptides containing an Arg(Tos) residue with HF, NMR and fluorescence experiments showed that by‐products were compounds in which a pyrenyl group was modified with a tosyl group(s). The side reaction was little suppressed by the addition of usual scavengers such as anisole, 1,2‐ethanedithiol, thioanisole andp‐cresol. Under the conditions used for the cleavage of Nα‐Boc group, i.e., trifluoroacetic acid or 4mHCl in dioxane, the pyrenylalanine residue was stable. No side reaction was, furthermore, observed in the reductive cleavage with sodium in liquid ammonia. These results suggest that the side reaction may be due to an electrophilic attack of tosyl cations to the electron‐rich pyrenyl group in the pyrenylalanine residue under the HF‐mediated
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb01308.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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10. |
High‐performance liquid chromatography of 2,4‐disubstituted‐5(4H)‐oxazolones, anhydrides and other activated forms ofN‐acyl‐ andN‐alkoxycarbonylamino acids |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 5,
1990,
Page 476-479
FRANCIS M.F. CHEN,
N. LEO BENOITON,
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摘要:
Normal phase high‐performance liquid chromatography has been achieved of the common activated forms of valine on a LiChrosorb‐CN or a μPorasil (underivatized silica) column using hexane containing 1.5 or 5%tert.‐butanol as solvent. Compounds examined include the 2‐alkoxy‐5(4H)‐oxazolones and symmetrical and mixed anhydrides ofN‐tert.‐butoxycarbonyl‐,N‐benzyloxycarbonyl‐, andN‐9‐fluorenylmethoxycar‐bonylvaline, the chloride of the latter, ap‐nitrophenyl ester, 2‐methyl‐4‐isopropyl‐5(4H)‐oxazolone, valine‐N‐carboxyanhydride, and theN‐ andO‐ethoxycarbonyl adducts of 1‐hydroxybenzotriazole. The 5(4H)‐ox‐azolones fromN‐tert.‐butoxycarbonylvaline andN‐benzyloxycarbonylglycylvaline decomposed during chromatography on the μPorasil but not the LiChrosorb‐CN column. The method allows direct monitoring of reactions involv
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb01309.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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