共查询到20条相似文献,搜索用时 46 毫秒
1.
N Yanihara K Tsuji C Yanaihara T Hashimoto T Kaneko A Arimura A V Schally 《Biochemical and biophysical research communications》1973,51(1):165-173
Syntheses are described of [Pro1]-LH-RH, [Orotic acid1]-LH-RH, [Glu1]-LH-RH, [Ser2]-LH-RH, [Leu2]-LH-RH, [Gln2]-LH-RH and [Phe2]-LH-RH. The LH-releasing hormone (LH-RH) activity of each of these peptides was compared with that of natural LH-RH . [Glu1]-LH-RH and [Phe2]-LH-RH had significant LH-RH activity, while all the other analogs possessed extremely low activities. These findings are briefly discussed in the light of the structure-activity relationship for LH-RH. 相似文献
2.
Synthesis and biological properties of (Leu-6)-LH-RH and (D-Leu-6,desGly-NH210)-LH-RH ethylamide 总被引:1,自引:0,他引:1
J A Vilchez-Martinez D H Coy A Arimura E J Coy Y Hirotsu A V Schally 《Biochemical and biophysical research communications》1974,59(4):1226-1232
[Leu6,desGly-NH210]-LH-RH ethylamide and [Leu6]-LH-RH, two analogs of LH-RH, were prepared by the solid phase method. LH- and FSH-releasing activity of these peptides was assayed against LH-RH by subcutaneous administration in immature male rats. When the integrated levels of LH and FSH over a 6 hr period after the injection were used as parameter of the LH- and FSH-releasing activities, the [Leu6]-LH-RH showed LH-releasing activity of 9 times and FSH-releasing activity of 5 times greater than that of LH-RH. [Leu6,desGly-NH210]-LH-RH ethylamide showed LH- and FSH-releasing activities of 53.6 and 14.5 times greater, respectively, than that of LH-RH. 相似文献
3.
D H Coy E J Coy A V Schally J Vilchez-Martinez Y Hirotsu A Arimura 《Biochemical and biophysical research communications》1974,57(2):335-340
A nonapeptide analog of luteinizing hormone-releasing hormone (LH-RH), [D-Ala6, des-Gly-NH210]-LH-RH ethylamide, was prepared by solid-phase methodology. The peptide was assayed against LH-RH in two systems and was found to be many times more potent than the naturally occurring hormone. In one of the tests, based on elevation of LH and FSH levels after infusion into immature male rats, the analog showed LH-releasing activity of 1600% and FSH-releasing activity of 1200% compared to LH-RH. 相似文献
4.
E Pedroza J A Vilchez-Martinez D H Coy A Arimura A V Schally 《Biochemical and biophysical research communications》1980,95(3):1056-1062
The ability of the Luteinizing Hormone-Releasing Hormone (LH-RH) analogs to displace LH-RH from its pituitary receptors was evaluated . The two superactive analogs tested showed higher potency than the antagonists and LH-RH itself, D-Trp6-LH-RH being the most potent. The LH-RH specific binding activity in the pituitary fluctuated throughout the age of the rats. The highest number of LH-RH binding sites were seen on day 35 of age (276 fmol × 10?2/pit) and an increment was induced by 0.05 μg D-Trp6-LH-RH (400 fmol × 10?2/pit). However, 1 μg D-Trp6-LH-RH reduced the binding of LH-RH at all the times studied. In the control animals the number of estradiol binding sites increased on day 42 of age, and 0.05 μg D-Trp6-LH-RH augmented them on day 35 of age. On the contrary, 1 μg D-Trp6-LH-RH diminished the estradiol uterine receptors at all the times studied. Similar results were obtained in the ovariectomized-hypophysectomized rats on day 35 of age. Our studies demonstrated a biphasic action of D-Trp6-LH-RH on LH-RH pituitary receptors and a direct effect on uterus which could be mediated through the uterine estradiol receptors. 相似文献
5.
T Wasiak J Humphries K Folkers C Y Bowers 《Biochemical and biophysical research communications》1979,86(3):843-848
A linear analogue of the luteinizing hormone-releasing hormone, longer than a decapeptide, is described for the first time, which is equivalent in potency to the best known inhibitors of ovulation, and which constitutes an important new lead to the design of inhibitors of even greater potency. At a dosage of 200 μg/rat, the undecapeptide [(1, -Phe2, -Trp3, -Trp6]-LH-RH caused 100% inhibition of ovulation. The related analogues, [(1, -Phe2, -Trp3, -Trp6]-LH-RH and [(Gly-Pro)1, -Phe2, -Trp3, -Trp6]-LH-RH, were less active, . All of these undecapeptides inhibited the action of 0.6 ng/ml of LH-RH by greater than 50% at the very low level of 10 ng/ml. 相似文献
6.
7.
Martin D. Hynes Mary Ann Lochner Kerry G. Bemis David L. Hymson 《Life sciences》1983,33(23):2331-2337
The binding characteristics of the delta opioid receptor ligand, 3HDAla2DLeu5 enkephalin, were markedly altered in brains obtained from mice fed an ethanol-containing diet for five days. Control mice exhibited both a high and low affinity site for 3HDAla2DLeu5 enkephalin, whereas those consuming the ethanol diet were found to possess only one binding site. This singular site has an intermediate KD value with an increase in receptor number when compared to the high and low affinity sites observed in control mice. The addition of ethanol to a brain membrane preparation obtained from untreated mice, at a concentration equivalent to that found in the blood of the ethanol-treated mice, did not markedly affect DAla2DLeu5 enkephalin binding characteristics. No alteration in the binding characteristics of 3H-naloxone, a mu receptor ligand, was noted following five days of ethanol consumption. Mice maintained on the ethanol-containing diet were tolerant to the activity-stimulating effects of acute ethanol administration. These results suggest that mice consuming an ethanol diet in sufficient quantities to render them tolerant exhibit a specific loss of a 3HDAla2DLeu5 enkephalin binding site, while the binding of 3H-naloxone was unchanged. 相似文献
8.
Some analogs of luteinizing hormone releasing hormone (LH-RH) having intense ovulation-inducing activity 总被引:1,自引:0,他引:1
M Fujino I Yamazaki S Kobayashi T Fukuda S Shinagawa W F White R H Rippel 《Biochemical and biophysical research communications》1974,57(4):1248-1256
Five new analogs of luteinizing hormone releasing hormone (LH-RH), des-Gly10-[Ala6]-LH-RH-ethylamide, des-Gly10-[D-Ala6]-LH-RH-ethylamide, des-Gly10-[α-aminoisobutyric acid6]-LH-RH-ethylamide, des-Gly10-[Phe5, D-Ala6]-LH-RH-ethylamide and des-Gly10-[Ile5, D-Ala6]-LH-RH-ethylamide were synthesized and evaluated for the ovulation-inducing activity in the rat, and it was found that the analogs, des-Gly10-[D-Ala6]-LH-RH-ethylamide and des-Gly10-[Phe5, D-Ala6]-LH-RH-ethylamide, were 50 times or more active than the original molecule. 相似文献
9.
D.H. Coy F.Labrie.M. Savary E.J. Coy A.V. Schally 《Biochemical and biophysical research communications》1975,67(2):576-582
The LH-releasing activity of eight superactive analogs of LH-RH was measured in pituitary cells in primary culture. Introduction of the C-terminal ethylamide modification into [D-Ala6]- and [D-Leu6]-LH-RH (two peptides already 3 times more active than LH-RH) increases their activities 10-fold. [D-Phe6]- and [D-Trp6]-LH-RH are 90 and 100 times more active than LH-RH, respectively. The ethylamide derivatives of these two compounds are however approximately six times less active than the parent peptides. 相似文献
10.
Acylated des-(Ala1-Gly2)-somatostatin analogs: prolonged inhibition of growth hormone secretion 总被引:1,自引:0,他引:1
P Brazeau W Vale J Rivier R Guillemin 《Biochemical and biophysical research communications》1974,60(4):1202-1207
The following eight analogs of somatostatin were synthesized by solid phase: des-[Ala1-Gly2]-somatostatin (I); des-[Ala1-Gly2]-H2somatostatin (II); -acetyl-Cys3-somatostatin (III); -acetyl-Cys3-H2somatostatin (IV); -pyvalyl-Cys3-H2somatostatin (V); -acrylyl-Cys3-H2somatostatin (VI); -benzoyl-Cys3-H2somatostatin (VII); -hexanoyl-Cys3-H2somatostatin (VIII). Deletion of the N-terminal dipeptide Ala1-Gly2 is compatible with high biological activity. A single s.c. injection of these analogs as a microsuspension in saline inhibits for 24–72 hours (depending on the compound) the secretion of growth hormone normally stimulated in rats by pentobarbital. 相似文献
11.
Adriana Farias Silva Erick Leite Bastos Marcelo Der Torossian Torres André Luis Costa‐da‐Silva Rafaella Sayuri Ioshino Margareth Lara Capurro Flávio Lopes Alves Antonio Miranda Renata de Freitas Fischer Vieira Vani Xavier Oliveira Jr. 《Journal of peptide science》2014,20(8):640-648
Angiotensin II (AII) as well as analog peptides shows antimalarial activity against Plasmodium gallinaceum and Plasmodium falciparum, but the exact mechanism of action is still unknown. This work presents the solid‐phase synthesis and characterization of eight peptides corresponding to the alanine scanning series of AII plus the amide‐capped derivative and the evaluation of the antiplasmodial activity of these peptides against mature P. gallinaceum sporozoites. The Ala screening data indicates that the replacement of either the Ile5 or the His6 residues causes minor effects on the in vitro antiplasmodial activity compared with AII, i.e. AII (88%), [Ala6]‐AII (79%), and [Ala5]‐AII (75%). Analogs [Ala3]‐AII, [Ala1]‐AII, and AII‐NH2 showed antiplasmodial activity around 65%, whereas the activity of the [Ala8]‐AII, [Ala7]‐AII, [Ala4]‐AII, and [Ala2]‐AII analogs is lower than 45%. Circular dichroism data suggest that AII and the most active analogs adopt a β‐fold conformation in different solutions. All AII analogs, except [Ala4]‐AII and [Ala8]‐AII, show contractile responses and interact with the AT1 receptor, [Ala5]‐AII and [Ala6]‐AII. In conclusion, this approach is helpful to understand the contribution of each amino acid residue to the bioactivity of AII, opening new perspectives toward the design of new sporozoiticidal compounds. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
12.
A F Spatola N S Agarwal A L Bettag J A Yankeelov C Y Bowers W W Vale 《Biochemical and biophysical research communications》1980,97(3):1014-1023
Using solid phase methods, seven agonist and antagonist analogues of LH-RH have been prepared containing enzyme-resistant CH2S linkages as selected amide bond replacements. Agonists modified at the 5–6, 6–7 and 9–10 position had 2, < 0.1, and 10% of the activity of LH-RH, respectively. Among potential antagonists, 6–7 position analogues showed only minimal inhibitory activity but N- and C-terminal modified analogues retained substantial LH-RH-LH and FSH inhibitory activity. In addition, a 1–2 position methylene thioether analogue of the parent [Ac-Pro1, D-Phe2, D-Trp3,6]LH-RH antagonist was completely inhibitory at 30 ng and represents the first such structure-modification that may be at least as active as its corresponding amide linked congener. However, neither 1–2 nor 9–10 methylene thioether position antagonists showed antiovulatory activity at the 250 μg level. 相似文献
13.
E Pedroza J A Vilchez-Martinez J Fishback A Arimura A V Schally 《Biochemical and biophysical research communications》1977,79(1):234-238
Competition for luteinizing hormone-releasing hormone (LH-RH) receptor sites by the inhibitory analog [D-Phe2, D-Trp3, D-Phe6]-LH-RH and by the superactive stimulatory analog [D-Trp6]-LH-RH was observed in adenohypophysial homogenates incubated at 4°C. Competition for LH-RH binding sites was less evident with adenohypophysial plasma membranes. The binding affinities of these analogues to LH-RH pituitary receptors can explain at least in part their respective action in blocking ovulation and in inducing a greater release of luteinizing hormone and follicle stimulating hormone than the parent hormone. 相似文献
14.
Ignacy Z. Siemion Zbigniew Szewczuk Zbigniew S. Herman Zdzislaw Stachura 《Molecular and cellular biochemistry》1981,34(1):23-29
Summary A semi-rigid structural analog of [Leu5] enkephalin, possessing the azo-bridge between Tyr1 and Phe4 residues, was synthesized, along with two other linear enkephalin analogs: [4′-amino Phe4] enkephalin and [4′hydroxyphenyl/-azo Phe4] enkephalin. The results of the determination of the analgesic activity of the synthesized compounds suggest that the biologically
active conformation of the enkephalin molecule should be such that both aromatic rings, Tyr1 and Phe4, are situated in close proximity. 相似文献
15.
J Humphries T Wasiak Y P Wan K Folkers C Y Bowers 《Biochemical and biophysical research communications》1978,85(2):709-713
Ac-[Pro1, , -Trp3, -Trp6]-LH-RH completely inhibited ovulation in cycling rats at 200μg/rat and is comparable in activity to the corresponding D-1-analogue. This Ac-Pro1-analogue is the most potent antiovulatory peptide yet known having an -amino acid residue in position 1. This result shows that for the design of potent inhibitors of ovulation, a -amino acid residue is not essential in position 1. The corresponding Ac--Pro1- and Kic1-analogues completely inhibited ovulation at 750μg/rat, but not at 200μg/rat, and the Cpc1-analogue was inactive at these dosages. 相似文献
16.
J R Giglio 《Analytical biochemistry》1975,69(1):207-221
The neurotoxin crotamine, which is a basic low molecular weight protein, was isolated, in the form of its hydrochloride, from a South Brazilian rattlesnake (Crotalus durissus crotaminicus, Crotalus durissus terrificus) venom.Disc electrophoresis, carried out in 7% acrylamide by the method of Reisfeld, at pH 4.5, showed a single band for the purified toxin.The toxin showed the following amino acid composition: Asx2, Ser3, Glx2, Pro3, Gly5, Cys5, Met1, Ileu1, Leu1, Tyr1, Phe2, Trp2, Lys9, His2, and Arg2, which corresponds to a minimum molecular weight of 4760. This assignment of minimum molecular weight is supported by the recovery of 1.0 mole of N-terminal of crotamine by the Sanger dinitrophenol (DNP) method, 1.0 mole of by the Udenfriend method, and by uv analysis, which gave a value of 4820. The odd number of half-cystine residues () cannot be explained on the basis of available analytical data.Tyrosine was the only amino-terminal residue detectable by the Sanger DNP method. Glycine was identified as the only carboxyl-terminal residue by the hydrazinolysis method of Akabori and by release upon treatment with yeast carboxypeptidase.The H+ electrometric and Cl? complexometric titrations of crotamine hydrochloride showed that about 13 moles of HCl are bound per 4760 g of the free base. 相似文献
17.
Y Okada K Kitamura Y Baba A Arimura A V Schally 《Biochemical and biophysical research communications》1973,53(4):1180-1186
Six analogs of LH-RH lacking N-terminal pGlu ring structure, Gly1-LH-RH, formyl Gly1-LH-RH, acetyl Gly1-LH-RH, propionyl Gly1-LH-RH, palmitoyl Gly1-LH-RH and acetyl Ala1-LH-RH were synthesized. The Gly1 analog was inactive, whereas acyl Gly1 analogs except palmitoyl Gly1 analog showed small but significant LH-RH activity in spite of the lack of the pyrrolidone ring structure. These findings suggest that the -CO-NHCHCO- group is the minimum necessary part of the pGlu residue to exhibit the biological activity. 相似文献
18.
Anton Iershov Konstantin Odynets Alexander Kornelyuk Vadim Kavsan 《Central European Journal of Biology》2010,5(4):407-420
The human genome encodes six proteins of family 18 glycosyl hydrolases, two active chitinases and four chitinase-like lectins
(chi-lectins) lacking catalytic activity. The present article is dedicated to homology modeling of 3D structure of human chitinase
3-like 2 protein (CHI3L2), which is overexpressed in glial brain tumors, and its structural comparison with homologous chi-lectin
CHI3L1. Two crystal structures of CHI3L1 in free state (Protein Data Bank codes 1HJX and 1NWR) were used as structural templates
for the homology modeling by Modeller 9.7 program, and the best quality model structure was selected from the obtained model
ensemble. Analysis of potential oligosaccharide-binding groove structures of CHI3L1 and CHI3L2 revealed significant differences
between these two homologous proteins. 8 of 19 amino acid residues important for ligand binding are substituted in CHI3L2:
Tyr34/Asp39, Trp69/Lys74, Trp71/Lys76, Trp99/Tyr104, Asn100/Leu105, Met204/Leu210, Tyr206/Phe212 and Arg263/His271. The differences between these residues could influence the structure of the ligand-binding groove and substantially change
the ability of CHI3L2 to bind oligosaccharide ligands. 相似文献
19.
Ken Inouye Kunio Watanabe Yoshihiro Tochino Masashi Kobayashi Yukio Shigeta 《Biopolymers》1981,20(9):1845-1858
The trypsin-catalyzed coupling of bovine (Boc)2-desoctapeptide (B23-B30)-insulin with synthetic octapeptides, H-Gly-X2-X3-X4-Thr-Pro-Lys(Boc)-Thr-OH (X2 = Phe or Ala, X3 = Phe or Ala, X4 = Tyr or Ala), followed by deprotection and purification produced the [AlaB24, ThrB30]-, [AlaB25, ThrB30]-, and [AlaB26, ThrB30]-analogs of bovine insulin in yields of 32, 35, and 32%, respectively. The biological activity of these analogs decreased in the order, normal insulin ([ThrB30]-bovine insulin) = AlaB26-insulin > AlaB25-insulin > AlaB24-insulin, as assayed for receptor binding and some other biological effects, in contrast with the corresponding Leu-analogs of human insulin, in which the activity decreased in the order, normal insulin > LeuB24-insulin > LeuB25-insulin. The affinity to insulin antibodies greatly diminished in both AlaB24-insulin and LeuB24-insulin but not in the B25-substituted analogs. The CD spectra of the Leu- and the Ala-analogs were compared with those of normal insulins to show that no apparent correlation seems to exist between the decrease in biological activity and the conformational changes observed in solution. The effects of organic solvents on the peptide-bond equilibrium and on the stability of trypsin are also discussed. 相似文献
20.
Y Masui T Tanaka N Chino H Kita S Sakakibara 《Biochemical and biophysical research communications》1979,86(4):982-987
Analogs of the mating factor of , Trp1- Trp3-Leu-Gln-Leu6-Lys7-Pro8-Gly-Gln-Pro11-Met12-Tyr13, from which amino acids were eliminated or substituted for other amino acid, were synthesized. These analogs showed lower biological activity than the natural mating factor if assayed after 6 hours incubation with -mating type cells of . However, if assayed after 24 or 48 hours incubation, the situation changed, i.e. the analogs in which Leu6 or Lys7 were replaced by the corresponding D-isomer, showed higher mating factor activity than the unsubstituted mating factor. The same result was obtained with the analogs in which Met was replaced by norleucine. 相似文献