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1. |
Structure and immunological properties of thymosin β9Met, a new analog of thymosin β4isolated from porcine thymus |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 6,
1990,
Page 481-488
TERESA L.K. LOW,
CHING‐YUANG LIN,
TAIR‐LONG PAN,
AIH‐JING CHIOU,
AKIRA TSUGITA,
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摘要:
During the course for the studies of thymosin β4and prothymosin α from porcine thymus, a new analog of thymosin β4has been identified. This peptide consists of 41 amino acid residues. The amino terminus is blocked by an acetyl group as revealed by fast atom bombardment mass spectrometric analysis. Amino acid sequence studies disclosed that this peptide is identical to bovine thymosin β9except that leucine at position 6 in β9is substituted by methionine. Thus, this new peptide has been termed thymosin β9Met. The recoveries of β9Met, β4, and prothymosin α in porcine tissues have been determined (inμg/gtissue) as follows: thymus (43, 85, 133); spleen (68, 203, 37); liver (10, 31, 27); heart (1.5, 10, 0); kidney (5, 51, 37); brain (0.8, 31, 5). Biologically, thymosin β9Met was found to be more active than β4in enhancing γ‐interferon production in cord blood lymphocytes. However, β4appeared to stimulate higher amounts of interleukin 2 and tumor necrotic factor. The significance for the coexistence of two homologous peptides with similar functions in the thymus and a number of other organs is not clear, and deserves furthe
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb00986.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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2. |
Crystal and molecular structure of two geometrically restricted chemotactic tripeptides, analogues of formyl‐methionine‐leucine‐phenylalanine* |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 6,
1990,
Page 489-498
ANDRÉ G. MICHEL,
GILLES LAJOIE,
CHAKIB AMEZIANE HASSANI,
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摘要:
The crystal structures of HCO‐Met‐Leu‐Phe‐OC(CH3)3, (CH25H39N3O5S),fMLP‐OtBu, and HCO‐Metψ[CSNH]‐Leu‐Phe‐OCH3, (C33H33N3O4S2),fMSLP‐OMe, have been determined by single crystal X‐ray diffraction, and their conformational properties investigated by molecular mechanics energy calculations. Crystals offMLP‐OtBuare monoclinic, space group P21, a = 12.027(4), b = 9.492(3), c = 12.660(4) Å, β= 101.99(3)°, Z = 2; those offMSLP‐OMeare orthorhombic, space group P212121, a = 7.130(1), b = 12.097(2), c = 31.060(5) Å, Z = 4. The first compoundsfMLP‐OtBuis the t‐butyl ester of the tripeptidefMLPthat represents one of the most potent compounds in inducing the lysozyme release from human neutrophils that reflects the chemotactic activity. From the crystal structure, it is shown that the orientation of the phenylalanine side chain is largely affected by the presence of the bulky group.fMSLP‐OMewas shown to be inactive after thionation of the methionine residue in the original tripeptide. Nevertheless, the crystal structure does not reveal any influence of the presence of the thionated peptidic bond on the backbone conformation. The X‐ray results have been used to generate parameters for empirical energy calculations. Subsequently, a strategy based on random generation of conformations followed by energy‐minimization was applied to investigate the conformational space of thiopeptides, in comparison with normal peptides. From molecular free energy calculations, it is shown that the main influence of the introduction of a thioamide bond on the molecular structure is to prevent the existence of C7eqconformations involving the thiomethionine residue. Consequently, a larger number of conformers are found to form intramolecular hydrogen bonds involving the formyl group, reducing its availability to interact with the receptor. For the first time, the theoretical prediction of the existence of C7eqconformations forfMLPis made. The resulting conformers are compared to previously activ
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb00987.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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3. |
Synthesis andin vitroandin vivoactivity of analogs of growth hormone‐releasing hormone (GH‐RH) withC‐terminal agmatine |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 6,
1990,
Page 499-505
MARTA ZARANDI,
VALER CSERNUS,
LAZARO BOKSER,
SANDOR BAJUSZ,
KATE GROOT,
ANDREW V. SCHALLY,
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摘要:
In the search for more active analogs of human growth hormone‐releasing hormone (GH‐RH), 37 new compounds were synthesized by solid phase methodology, purified, and tested biologically. Most of the analogs contained a sequence of 27 amino acids andN‐terminal desaminotyrosine (Dat) andC‐terminal agmatine (Agm), which are not amino acids. In addition to Dat in position 1 and Agm in position 29, the majority of the analogs had Ala15and Nle27substitutions and one or more additional L‐ or D‐amino acid modifications. [Dat1, Ala15, Nle27]GH‐RH(1‐28)Agm (MZ‐2‐51) was the most active analog. Itsin vitroGH‐releasing potency was 10.5 times higher than that of GH‐RH(1‐29)NH2and in the i.v.in vivoassay, MZ‐2‐51 was 4‐5 times more active than the standard. After s.c. administration to rats, MZ‐2‐51 showed an activity 34 times higher at 15min and 179 times greater at 30min than GH‐RH(1‐29)NH2and also displayed a prolonged activity. D‐Tyr10, D‐Lys12, and D‐Lys12homologs of MZ‐2‐51 also showed enhanced activities. Thus, [Dat1, D‐Tyr10, Ala15, Nle27]GH‐RH(1‐28)Agm (MZ‐2‐159), [Dat1, D‐Lys12, Ala15, Nle27]GH‐RH(1‐28)AGM (MZ‐2‐57), and [Dat1, Ala15, D‐Lys21, Nle27]GH‐RH(1‐28)Agm (MZ‐2‐75) were 4‐6 times more activein vitrothan GH‐RH(1‐29)NH2.In vivo, after i.v. administration, analog MZ‐2‐75 was equipotent and analogs MZ‐2‐159 and MZ‐2‐57 about twice as potent as the standard. After S.C. administration, the potencies of MZ‐2‐57 and MZ‐2‐75 were 10‐14 times higher than the standard at 15 min and 45‐89 times greater when determined at 30 min. Most of the analogs containing two or more D‐amino acid substitutions were less active than GH‐RH(1‐29)NH2or inactive. Our studies indicate
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb00988.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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4. |
Peptides related to the active fragment of “proline rich polypeptide”, an immunoregulatory protein of the ovine colostrums |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 6,
1990,
Page 506-514
IGNACY Z. SIEMION,
GERD FOLKERS,
ZBIGNIEW SZEWCZUK,
ANDRZEJ JANKOWSKI,
ALEKSANDRA KUBIK,
WOLFGANG VOELTER,
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摘要:
The preferred solution conformation of the PRP‐hexapeptide (Tyr‐Val‐Pro‐Leu‐Phe‐Pro) and of some of its structural analogues was investigated by NMR‐ spectroscopy, spectrofluorimetry and computer simulation technic. It was found that the preferred conformation is characterized bycis′‐conformation of Pro3and the γ‐turn on the Leu4‐residue: for Val2and Phe5a β‐structure seems to be privileged. In such a conformation Val2and Leu4residues occupy exactly the same positions in space as residuesiandi+ 3 in an α‐helix. It suggests that the PRP‐hexapeptide can interact with receptor protein inducing or stabilizing its helical conformation
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb00989.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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5. |
Synthetic, immunological and structural studies on repeat unit peptides ofPlasmodium falciparumantigens |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 6,
1990,
Page 515-521
PARAMJEET KAUR,
PAWAN SHARMA,
A. KUMAR,
V.S. CHAUHAN,
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摘要:
Using solid phase methodology, we have synthesized five peptides (16‐18 residues long) corresponding to repeat sequences of four antigens of a human malarial parasite,Plasmodium falciparum.Three of these antigens (RESA, FIRA, and ABRA) are found in the asexual blood‐stages of the parasite, while the remaining one (CSP) is found in the sporozoites. The synthetic peptides, conjugated to bovine serum albumin, elicited high levels of antibodies in rabbits, and these antibodies were found to cross‐react with the heterologous peptides. The degree of cross‐reactivity, as estimated in an ELISA, was quite remarkable among all the peptides. The peptide corresponding to the RESA tetrapeptide repeat was found to be the most immunogenic and highly cross‐reactive. For this reason this tetrapeptide repeat unit, peptide 1, may be a suitable candidate for inclusion in a multiple epitope polypeptide vaccine design. Conformational studies using circular dichroism spectroscopy show that these peptides have similar conformational characteristics with a common feature OF ∼30% and ∼50% helical content in water and TFE respectively. Theoretical predictions regarding conformation using the Chou‐Fasman method have also
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb00990.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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6. |
Neuropeptide Y: identification of the binding site |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 6,
1990,
Page 522-530
ANNETTE G. BECK‐SICKINGER,
WOLFRAM GAIDA,
GERD SCHNORRENBERG,
RUDOLPH LANG,
GÜNTHER JUNG,
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摘要:
Based on the hypothetical 3D structure of neuropeptide Y (NPY), NPY 1‐4‐Aca‐25‐36, a 17 amino acid analogue, has been synthesized replacing the sequence NPY 5‐24 by ε‐aminocaproic acid (Aca). This low‐molecular weight deletion analogue showed nearly comparable receptor affinity to NPY. In order to elucidate the structural requirements for receptor recognition each amino acid of 1‐4‐Aca‐25‐36 was exchanged by its D‐enantiomer, glycine and L‐alanine. In addition distinct amino acids were replaced by closely related residues. Multiple peptide synthesis was applied using Fmoc‐strategy and BOP activation. Binding assay was performed on rabbit kidney membrane preparations. The results of structure affinity studies suggest that the C‐terminal tetrapeptide NPY 33‐36 is es
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb00991.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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7. |
Synthesis and crystal structures of Boc‐L‐Asn‐L‐Pro‐OBzl·CH3OH and dehydration side product, Boc‐β‐cyano‐L‐alanine‐L‐Pro‐OBzl |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 6,
1990,
Page 531-537
A.N. STROUP,
L.B. COLE,
M.M. DHINGRA,
L.M. GIERASCH,
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摘要:
Boc‐L‐Asn‐L‐Pro‐OBzl:C21H29O6N3·CH3OH, Mr= 419.48 + CH3OH, monoclinic, P21,a= 10.049(1),b= 10.399(2),c= 11.702(1)Åβ= 92.50(1)°, V = 1221.7(3)Å3, dx= 1.14g cm‐3, Z = 2, CuKα (λ= 1.54178 Å), F(000) = 484 (with solvent), 23°, unique reflections (I>3σ(I)) = 1745, R = 0.043, Rw= 0.062, S = 1.66. Boc‐β‐cyano‐L‐alanine‐L‐Pro‐OBzl: C21H27O5N3, Mr= 401.46, orthorhombic, P212121,a= 15.741(3),b= 21.060(3),c= 6.496(3)ÅV= 2153(1)Å3, dx= 1.24g·cm‐3, Z = 4, CuKα (λ= 1.54178 Å), F(000) = 856, 23°, unique reflections (I>3σ(I)) = 1573, R = 0.055, Rw= 0.078, S = 1.86. Thetert.‐butyloxycarbonyl (Boc) protected dipeptide benzyl ester (OBzl), BOC‐L‐Asn‐L‐Pro‐OBzl, prepared from a mixed anhydride reaction using isobutylchloroformate, BOC‐L‐asparagine, and HCI·L‐proline‐OBzl, crystallized with one methanol per asymmetric unit in an extended conformation with the Asn‐Pro peptide bondtrans.Intermolecular hydrogen bonding occurs between the methanol and the Asn side chain and between the peptide backbone and the Asn side chain. A minor impurity due to the dehydration of the Asn side chain to a β‐CNaia crystallized with a
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb00992.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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8. |
Synthesis of [β‐(4‐pyridyl‐1‐oxide)‐L‐alanine4]‐angiotensin I as a potential suicide substrate for protein‐tyrosine kinases |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 6,
1990,
Page 538-543
MARK CUSHMAN,
PENNAMUTHIRIAR CHINNASAMY,
ASIT K. CHAKRABORTI,
JURJUS JURAYJ,
ROBERT L. GEAHLEN,
RUDIGER D. HAUGWITZ,
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摘要:
An asymmetric synthesis of [β‐(4‐pyridyl‐1‐oxide)‐L‐alanine4]‐angiotensin I (la), which is a potential suicide substrate (mechanism‐based inhibitor) for protein‐tyrosine kinases, has been performed. Deprotonation of 6 withn‐butyllithium in THF gave the anion 7, which was alkylated with 4‐(chloromethyl)pyridine‐1‐oxide to afford intermediate 9 as a crystalline solid. Hydrolysis of 9 afforded a mixture of 11 and 12 in a ratio of 96:4 as estimated by conversion to the diastereomeric dipeptides 13 and 14 followed by HPLC analysis. The 96:4 mixture of 11 and 12 was used in the solid phase synthesis of the target angiotensin analog la and its diastereomer 1b, which were separated and tested for inhibitory activity against two thymocyte protein‐tyrosine kinases: p40and p56lck. Neither peptide displayed significant inhibitory activity toward p40 and both served as weak comp
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb00993.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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9. |
A simple, continuous fluorometric assay for HIV protease |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 6,
1990,
Page 544-550
MIHALY V. TOTH,
GARLAND R. MARSHALL,
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摘要:
Novel fluorogenic substrates for human immunodeficiency viral protease have been developed based on the principle of fluorescence energy transfer. Starting from a p24/p15 cleavage site‐derived hexapeptide substrate, Ac‐Thr‐Ile‐Nle‐Nle‐Gln‐Arg‐NH2, incorporation of 2‐aminobenzoic acid in place of the acetyl group as the donor andp‐NO2‐Phe at the P1′ position as acceptor gave the intramolecularly quenched fluorogenic substrate. Cleavage of the substrate by HIV protease released the fluorescentN‐terminal tripeptide from its close apposition to the quenching nitrobenzyl group, resulting in enhanced fluorescence. An automated assay based on 96=well microtiter plates and a fluorometric plate reader have been developed, which allow high throughput of compounds in the search fo
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb00994.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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10. |
Solid phase synthesis of the retro viral nucleocapsid protein NCp10 of Moloney Murine Leukaemia virus and related “zinc‐fingers” in free SH forms |
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International Journal of Peptide and Protein Research,
Volume 36,
Issue 6,
1990,
Page 551-558
FABRICE CORNILLE,
YVES MELY,
DAMIEN FICHEUX,
ISABELLE SAVIGNOL,
DOMINIQUE GERARD,
JEAN‐LUC DARLIX,
MARIE‐CLAUDE FOURNIE‐ZALUSKI,
BERNARD P. ROQUES,
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摘要:
The core of retroviruses contains a highly conserved, low molecular weight, basic protein that binds nucleic acids and is essential for genomic RNA packaging. The 56 amino acid protein, NCp10, of Moloney Murine Leukaemia virus (MoMuLV) has the CysX2CysX4HisX4Cys zinc finger‐like motif shared by all retrovirus nucleocapsid proteins. The native protein and five modified peptides containing the zinc binding domain were synthesized by solid phase in order to investigate the structural and biochemical role of Zn2+chelation in MoMuLV NCp10 activity. The purity of the synthetic molecules was verified by HPLC and their sequences were confirmed by amino acid analysis and sequencing in the case of NCp10. Thiol dosage agreed with the theoretical value of free cysteine for all these molecules. Fluorescence measurements performed on synthetic NCp10 and zinc finger fragments showed that the tryptophan quantum yield was Zn2+‐dependent allowing a 1:1 stoichiometry for the complex to be determined. The apparent affinity constant of NCp10 for the metal was estimated to be superior to 106M‐1. The synthetic protein, in the presence of Zn2+ions, possesses all the biological properties of NCp10 isolated from virions. It catalyzes both the MoMuLV RNA dimerization and the annealing of the replication primer tRNAProonto MoMuL
ISSN:0367-8377
DOI:10.1111/j.1399-3011.1990.tb00995.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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