共查询到20条相似文献,搜索用时 15 毫秒
1.
JAVIER SUEIRAS-DIAZ D. MICHAEL JONES MICHAEL SZELKE BRENDA J. LECKIE SHEILA R. BEATTIE C. BEATTIE JAMES J. MORTON 《Chemical biology & drug design》1997,50(4):239-247
Using solid-phase methodology we have synthesised peptides based on the 8–14 or 6–14 human and rat angiotensinogen sequences, containing the following different isosteric units at the P1-P1’cleavage site: Leu-Ψ[CH2NH]Leu; Leu-[CH(OH)CH2]Val; Leu-Ψ[CH(OH)CH2]Leu and Leu-Ψ[CH(NH2)CH2]Val. In vitro, peptide Piv-His-Pro-Phe-His-Leu-Ψ[CH(OH)CH2]Leu-Tyr-Tyr-Ser-NH2( XXI ) is the most potent inhibitor of rat plasma renin reported having an IC50 of 0.21 nM; it is a much weaker inhibitor of human renin (IC50 45 nM). Peptide Boc-His-Pro-Phe-His-Leu-Ψ[CH(OH)CH2] Leu-Val-Ile-His-NH2 ( XX ) was a highly effective inhibitor of rat renin in vivo. When infused (1 mg/kg/h) into two-kidney, one-clip chronic renal hypertensive rats, it lowered blood pressure and suppressed both plasma renin and angiotensin II. When given as a bolus (1 mg/kg) there was a divergence between the rapid rebound of renin levels and blood pressure, which remained suppressed. These results indicate that potent in vivo inhibitors of rat renin could be useful not only in examining the role of circulating renin but also in elucidating the equally important involvement of extracirculatory renin pools. 相似文献
2.
JEAN-ALAIN FEHRENTZ RENE SEYER ANNIE HEITZ PIERRE FULCRAND BERTRAND CASTRO PIERRE CORVOL 《Chemical biology & drug design》1986,28(6):628-636
The [Tyr40]preprorenin (40–50) peptide methyl ester, an undecapeptide related to the human renin prosegment, has been synthesized using a stepwise strategy with hydrogenolisable protections on the side chains. The final deprotection was very difficult as observed by 1 H NMR and reversed phase HPLC. 2D 1 H NMR spectroscopy of the purified peptide allowed the assignment of all protons. 相似文献
3.
JEAN-ALAIN FEHRENTZ RENE SEYER ANNIE HEITZ PIERRE FULCRAND BERTRAND CASTRO PIERRE CORVOL 《Chemical biology & drug design》1986,28(6):620-627
The [Tyr47, Nle53] preprorenin (47–60) peptide methyl ester, a tetradecapeptide related to the human renin prosegment, has been synthesized using a three-segment coupling strategy. Selective deprotection of the segments before coupling allowed an easy removal of the final tetradecapeptide side chain-protecting groups by acidolysis and an easy purification. Antibodies raised against this peptide bound the plasmatic inactive renin. 相似文献
4.
RAFFAELLA GARZIA DONALD YAMASHIRO R. GLENN HAMMONDS CHOH HAO LI 《Chemical biology & drug design》1982,19(4):432-435
Four analogs of human β-endorphin (βh-EP) were synthesized by the solid-phase method: βh-EP-(1–17) (I), [D-Ala2]-βh-EP-(1–17) (II), [Gln8]-βh-EP-(1–17) (III) and [D-Ala2, Gln8]-βh-EP-(1–17) (IV). Measurement in a radio-receptor binding assay with use of tritiated βh-EP as primary ligand gave relative potencies as follows: Met-enkephalin, 100; I, 33; II, 47; III, 889; IV, 123; βh-endorphin, 2253. 相似文献
5.
ROBERT JACQUIER RENE LAZARO HANTA RANIRISEHENO PH. VIALLEFONT 《Chemical biology & drug design》1987,30(1):22-32
In studies leading to HC toxin synthesis, a phytotoxic cyclic tetrapeptide with the sequence cyclo (L-Ala-D-Ala-L-Aoe-D-Pro), we have determined optimal conditions for the cyclization which constitutes one of the most important steps in the synthesis of the toxin. All four possible sequences containing an optically active precursor, i.e. L-Ada = (2 S)-2-amino-9-decenoic acid instead of Aoe, have been prepared and subjected to cyclization. Owing to the differences in racemization risk during activation of the terminal carboxyl aminoacid different cyclization procedures have been applied. Cyclopeptide yields and selectivity between cyclomonomer and dimer both containing the title sequence are mainly controlled by the linear precursor sequence. The cyclic tetrapeptide is only obtained with D-proline in the C-terminal position, the best yield reached by the -ONSu activation method. Starting from the peptide, the (9S, 9R) HC toxin epimer on the epoxidic carbon atom has been further synthesized in two steps. 相似文献
6.
YOSHIO OKADA YUKO TSUDA YOKO NAGAMATSU UTAKO OKAMOTO 《Chemical biology & drug design》1984,24(4):347-358
Stereoisomers of specific substrates for SFP and ELP, Suc-L-Tyr-L-Leu-L-Val-pNA and Suc-L-Ala-L-Tyr-L-Leu-L-Val-pNA, were synthesized by the conventional solution method. Suc-L-Tyr-D-Leu-D-Val-pNA was found to be an effective and specific inhibitor of SFP and ELP. Suc-L-Tyr-L-Leu-L-Val-Pipe and Suc-L-Tyr-D-Leu-D-Val-Pipe inhibited only SFP very slightly and showed no inhibitory effect on ELP. Both Dan-L-Tyr-L-Leu-L-Val-pNA and Dan-L-Tyr-D-Leu-D-Val-pNA exhibited an inhibitory effect on both SFP and ELP. 相似文献
7.
JAN IZDEBSKI JOLANTA BONDARUK S. WITOLD GUMUKA PAWE KRZA
CIK 《Chemical biology & drug design》1989,33(2):77-81
The dodecapeptide sequence, Tyr-Gly-Gly-Phe-Met-Lys-Arg-Tyr-Gly-Gly-Phe-Met (BI), which is totally conserved in the primary structures of human, bovine, rat, and toad preproenkephalins, has been synthesized by the solid-phase method. Coupling reactions were achieved by using symmetrical anhydrides of tert.-butyloxycarbonylamino acids preformed with N-tert.-butyl,N′-methylcarbodiimide. 6-Arg and 7-Lys analogs have also been obtained. The peptides show opiate activity in both GPI and MVD assay, and possess antinociceptive properties as estimated by the hot-plate test in mice when applied intracisternally. 相似文献
8.
HISAKAZU MIHARA SANNAMU LEE YASUYUKI SHIMOHIGASHI HARUHIKO AOYAGI TETSUO KATO NOBUO IZUMIYA TOMMASO COSTA 《Chemical biology & drug design》1987,30(5):605-612
The novel fluorescent amino acid, l -1-pyrenylalanine (l -Pya), was prepared by the asymmetric hydrogenation of cyclic dehydrodipeptide. Fluorescent enkephalins containing one or two Pya residues at position 1, 4 or 5 of [d -Ala2, Leu5]enkephalin were synthesized by the solution method. Mono-Pya-enkephalins showed strong fluorescence intensities and potent binding affinities with specificity and selectivity for opiate receptors. However, di-Pya-enkephalins showed markedly decreased receptor binding affinities. These results indicate that the incorporation of two Pya residues into enkephalin makes the peptide unable to interact with the opiate receptors, although introduction of one Pya residue is effective to elicit a specific receptor interaction. Di-Pya-enkephalins showed intramolecular excimer spectra, indicating that the peptides are able to take possible folded conformations. 相似文献
9.
人甲状旁腺素(1-34)的合成与聚乙二醇化修饰 总被引:2,自引:1,他引:2
目的合成人甲状旁腺素(1 34) [hPTH(1-34) ]并进行聚乙二醇化修饰。方法应用固相多肽合成方法合成并经高效液相色谱纯化得hPTH(1-34) ,Cys-hPTH(1- 34)和hPTH(1-34)-Cys-NH2 。Cys hPTH(1-34)和hPTH(1-34)-Cys-NH2 在水溶液(pH 7~8)中分别与平均相对分子质量为5 0 0 0的单甲氧基马来酰亚胺基聚乙二醇(mPEG50 0 0 MAL)反应,经高效液相色谱纯化得Cys(mPEG50 0 0 MAL)- hPTH(1-34)和hPTH(1-34)-Cys(mPEG50 0 0- MAL) -NH2 。结果hPTH(1-34) ,Cys(mPEG50 0 0 MAL) hPTH(1 34)和hPTH(1 34) Cys(mPEG50 0 0 MAL) NH2 的质谱和氨基酸组成分析结果均与理论值一致。hPTH(1-34) -Cys(mPEG50 0 0-MAL) NH2 保持了较好的体外活性,Cys(mPEG50 0 0- MAL) hPTH(1-34)保持了较好的体内活性。结论采用一种简便的方法成功实现了对hPTH(1-34)的N端或C端的聚乙二醇化修饰 相似文献
10.
DONALD YAMASHIRO RAFFAELLA GARZIA R. GLENN HAMMONDS CHOH HAO LI 《Chemical biology & drug design》1982,19(3):284-289
Four analogs of human β-endorphin (βh-EP) were synthesized by the solid-phase method: βh-EP-(1–9) (I), [D-Ala2]-βh-EP-(1–9) (II), [Gln8]-βh-EP-(1–9) (III), and [D-Ala2, Gln8]-βh-EP-(1–9) (IV). Measurement in a radioreceptor binding assay with use of tritiated βh-EP as primary ligand gave relative potencies as follows: Met-enkephalin, 100; I, 76; II, 100; III, 200; IV, 200. Two new amino acid derivatives were prepared and used for synthesis of the analogs: Nα-t-butyloxycarbonyl-O-(cyclopentyl) -tyrosine and Nα-t-butyloxycarbonyl-γ-(cyclopentyl)-glutamic acid. 相似文献
11.
目的:以氟康唑为先导化合物,设计合成新的三唑醇类化合物,并研究其抗真菌活性。方法:引入4位羧酸酯取代的苄基侧链结构,合成一系列目标化合物,所有化合物结构均经MS、^1H-NMR等谱确证;选择8种真菌为实验菌株,测定其体外抗真菌活性。结果:合成了15个未见文献报道的目标化合物;所有化合物对所选真菌均表现出了一定的抑菌活性,其中化合物(1),(2)和(3)对除薰烟曲霉菌外的7种菌都表现出了较好的抑菌活性。结论:4位羧酸酯取代的苄基侧链结构的引入对目标化合物的抗菌活性有一定的影响,侧链越短.抑菌活性越好. 相似文献
12.
目的:以氟康唑为先导化合物,设计合成新的三唑醇类化合物,并研究其抗真菌活性。方法:引入异丙基及取代氨基侧链结构,合成一系列目标化合物,所有化合物结构均经MS、^1H—NMR等谱确证;选择8种真菌为实验菌株,测定其体外抗真菌活性。结果:合成了15个目标化合物;所有化合物对所选真菌均表现出了一定的抑菌活性,其中化合物(6c),(6d),(6e),(6f)和(6g)对除薰烟曲霉菌外的7种菌株都表现出了较好的抑菌活性。结论:取代氨基侧链结构的引入对目标化合物的抗菌活性有一定的影响,侧链为取代苄基活性较好,且取代苄基侧链越短,抑菌活性越好。 相似文献
13.
1-(1,2,4-三唑-1H -1-基)-2-(2,4-二氟苯基)-3-(4-取代苄基-1-哌嗪基)-2-丙醇的合成及抗真菌活性 总被引:2,自引:0,他引:2
目的寻找广谱、高效、低毒的新一代三唑类抗真菌药物。方法根据靶酶活性位点的空腔大小、各种力场和关键残基分布,设计并合成了19个1-(1,2,4-三唑-1H -1-基)-2-(2,4-二氟苯基)-3-(4-取代苄基-1-哌嗪基)-2-丙醇类化合物,测定了体外抗真菌活性。结果所有化合物对8种致病真菌均有较强的抗真菌活性,对深部真菌的活性明显优于浅部真菌。结论绝大部分化合物的抗真菌活性明显高于氟康唑和特比萘芬,其中化合物VIII-1,10,12,17具有广谱、高活性的优点,值得进一步深入研究。 相似文献
14.
15.
SANDRA C. STORY THOMAS F. MURRAY GARY E. DELANDER JANE V. ALDRICH 《Chemical biology & drug design》1992,40(2):89-96
A series of 2-substituted dynorphin A-(1-13) amide (Dyn A-(1-13)NH2) analogues was prepared by solid phase peptide synthesis and evaluated for opioid receptor affinities in radioligand binding assays and for opioid activity in the guinea pig ileum (GPI) assay. Amino acid substitution at the 2 position produced marked differences in both opioid receptor affinities and potency in the GPI assay; Ki values for the analogues in the radioligand binding assays and IC50 values in the GPI assay varied over three to four orders of magnitude. The parent peptide, Dyn A-(1-13)NH2, exhibited the greatest affinity and selectivity for kappa receptors and was the most potent peptide examined in the GPI assay. The most important determinant of opioid receptor selectivity and opioid potency for the synthetic analogues was the stereochemistry of the amino acid at the 2 position. Except for [D-Lys2]Dyn A-(1-13)NH2 in the kappa receptor binding assay, the analogues containing a D-amino acid at position 2 were much more potent in all of the assays than their corresponding isomers containing an L-amino acid at this position. The L-amino acid-substituted analogues generally retained some selectivity for kappa opioid receptors. The more potent derivatives with a D-amino acid in position 2, however, preferentially interacted with mu opioid receptors. Introduction of a positively charged amino acid into the 2 position generally decreased opioid receptor affinities and potency in the GPI assay. 相似文献
16.
Observation of contradictory results with the in vitro assays for inhibin-like activity of the carboxyl terminal 28 amino acid peptide 67–94 with a disulfide loop, of human seminal plasma inhibin (HSPI), prompted us to synthesize both the linear and the cyclic peptides and test their ability to suppress the circulating levels of follicle stimulating hormone (FSH) in vivo in adult male rats. The linear peptide [Cys(Acm)73,87] 67–94 of HSPI was synthesized by solid-phase peptide synthesis using fluorenylmethyloxycarbonyl (Fmoc) chemistry and a continuous-flow technology. The peptide was cyclized by direct iodine oxidation of the S-diacetamidomethyl peptide in dilute solution. In the in vivo assay the linear peptide did not affect the levels of FSH, whereas the cyclic peptide suppressed the levels of FSH significantly. Thus, the carboxyl terminal region of HSPI does have inhibin-like activity and perhaps has the active core of the protein. 相似文献
17.
P. Fu S. Layfield T. Ferraro H. Tomiyama J. Hutson L. Otvos G.W. Tregear R.A.D. Bathgate J.D. Wade 《Chemical biology & drug design》2004,63(2):91-98
Abstract: Biotin‐avidin immobilization has been routinely used as a tool to study peptide–receptor and peptide–antibody interactions. Biotinylated peptides can also be employed to localize cells that express the peptides’ receptor, and to analyse ligand‐receptor binding. Insulin‐like peptide 3 (INSL3) is a peptide hormone which contains A‐ and B‐chains connected by two disulphide bonds and plays a role in testicular descent during sexual development. In order to study the interaction of INSL3 with its receptor LGR8, a G protein‐coupled receptor, we chemically synthesized Nα‐mono‐biotinylated human INSL3 (B‐hINSL3) and compared it structurally and biologically with hINSL3. Both peptides exhibited similar, but high, receptor binding affinities on human foetal kidney fibroblast 293T cells transfected human LGR8 based on a competition radioreceptor assay with 33P‐labelled relaxin H2 (B33). The modified B‐hINSL3 showed full biological activity as determined by the stimulation of gubernacular cell proliferation. The labelled B‐hINSL3 contains a higher α‐helix content, and this increased helical structure is accompanied by an increase in ability to stimulate cAMP accumulation in 293T cells expressing LGR8. Our results suggest that the N‐terminal region of the A‐chain is not involved in the interaction of INSL3 with its receptor. However, the introduction of biotin onto the N‐terminus of the A‐chain promoted conformational stability which, in turn, permitted better receptor activation. 相似文献
18.
KLEOMENIS BARLOS DIMITRIOS GATOS OLGA HATZI NICOLE KOCH SOFIA KOUTSOGIANNI 《Chemical biology & drug design》1996,47(3):148-153
S-4-methoxytrityl cysteine was synthesized and converted into the corresponding Fmoc-Cys(Mmt)-OH by its reaction with Fmoc-OSu. As compared to the corresponding Fmoc-Cys(Trt)-OH, the S-Mmt-function was found to be considerably more acid labile. Quantitative S-Mmt-removal occurs selectively in the presence of groups of the tert butyl type and S-Trt by treatment with 0.5–1.0% TFA. The new derivative was successfully utilized in the SPPS of Tyr1-somatostatin on 2-chlorotrityl resin. In this synthesis groups of the Trt-type were exclusively used for amino acid side-chain protection. Quantitative cleavage from the resin and complete deprotection was performed by treatment with 3% TFA in DCM–TES (95:5) for 30 min at RT. We observed no reduction of tryptophan under these conditions. © Munksgaard 1996. 相似文献
19.
H.P.J. BENNETT N.G. SEIDAH S. BENJANNET S. SOLOMON M. CHRETIEN 《Chemical biology & drug design》1986,27(3):306-313
The cystine bridge structure of the amino-terminal fragment of human proopiomelanocortin has been reinvestigated. Highly purified amino-terminal fragment 1–76 was rapidly isolated from human pituitaries using only reverse-phase liquid chromatography (RP-HPLC). This peptide was then subjected to trypsin and V8-protease digestion and the products separated by RP-HPLC> and subjected to amino acid and microsequence analysis. The results show that disulfide bridges link Cys-2 to Cys-24 and Cys-8 to Cys-20. Amino acid analysis and amino sugar determination confirm (i) the previously proposed sequence and (ii) the suggestion of the presence of two glycosylation sites in this molecule. These are most probably located at Thr-45 (O-glycosylation) and at Asn-65 (N-glycosylation). 相似文献
20.
YVAN BOULANGER YANMIN CHEN FERNANDO COMMODARI LOUIS SENCAL ANNE-MARIE LABERGE ALAIN FOURNIER SERGE ST-PIERRE 《Chemical biology & drug design》1995,45(1):86-95
The structures of human NPY and of its centrally truncated agonist analog [Ahx5–17]NPY have been investigated in DMSO-d6 by two-dimensional NMR and by molecular modeling. For both peptides, a complete resonance assignment was achieved and a large number (more than 200) of inter-residue NOE connectivities were observed, including long-range connectivities between the N- and C-terminal ends of the chain. Molecular models were calculated using NOE constraints by distance geometry, simulated annealing and conjugate gradient energy minimization. The results indicate that both peptides are folded in the center of their chain, NPY adopting the hairpin shape, whereas the central portion of [Ahx5–17]NPY is characterized by relatively large loops. In contrast to previous models, practically no α-helical structure exists for these peptides under our conditions, but two β-turns are found in NPY and one in [Ahx5–17]NPY. The proximity of the terminal ends could be the determinant factor for their activity. © Munksgaard 1995. 相似文献