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11.
The helicity of the tryptathionine moiety of the phallotoxins has been recognized by comparison with cyclic tryptathionine tripeptides. In order to investigate the influence of the configuration of the component amino acids on the conformation of the cyclic peptides, six analogue thioether tripeptides containing L- and D-alanine and L- and D-cysteine, respectively, have been synthesized. The CD spectra of the peptides are very similar to each other, showing mirror images of the CD of phalloidin and, therefore, negative helicity. The spectra of the D-cysteine containing compounds differ from the L-cysteine containing compounds by their weakly positive ellipticity values around 270 nm. The cyclization reaction of Boc-Hpi-D-Ala-D-Cys(STrt)OCH3, along with the cyclic tripeptide, afforded a cyclic hexapeptide by dimerization. The CD spectrum of the dimer is very similar to that of phalloidin, thus pointing to a positive helicity of its two tryptathionine moieties. The dimeric thioether peptide forms a rather strong complex with Cu2+ ions. 相似文献
12.
Cholecystokinin (CCK) is a putative peptide neurotransmitter present in high concentration in the cerebral cortex. By using techniques of in vitro receptor autoradiography, CCK binding sites in primate cortex were labeled with 125I-Bolton-Hunter-labeled CCK-33 (the 33-amino-acid C-terminal peptide) and 3H-CCK-8 (the C-terminal octapeptide). Biochemical studies performed on homogenized and slide-mounted tissue sections showed that the two ligands labeled a high-affinity, apparently single, saturable site. Autoradiography revealed that binding sites labeled by both ligands were anatomically indistinguishable and were distributed in two basic patterns. A faint and diffuse label characterized portions of medial prefrontal cortex, premotor and motor cortices, the superior parietal lobule, and the temporal pole. In other cortical areas the pattern of binding was layer-specific; i.e., binding sites were concentrated within particular cortical layers and were superimposed upon the background of diffuse label. Layer-specific label was found in the prefrontal cortex, anterior and posterior cingulate gyrus, somatosensory cortex, inferior parietal lobule, retrosplenial cortex, insula, temporal lobe cortices, and in the primary visual and adjacent visual association cortices. The areal and laminar localization of layer-specific CCK binding sites consistently coincided with the cortical projections of thalamic nuclei. In prefrontal cortex, CCK binding sites were present in layers III and IV, precisely paralleling the terminal fields of thalamocortical projections from the mediodorsal and medial pulvinar nucleus of the thalamus. In somatosensory cortex, the pattern of CCK binding in layer IV coincided with thalamic inputs arising from the ventrobasal complex, while in the posterior cingulate gyrus, insular cortex, and retrosplenial cortex, layer IV and lower III binding mirrored the laminar distribution of cortical afferents of the medial pulvinar. CCK binding in layers IVa, IVc alpha, IVc beta, and VI of primary visual cortex corresponded to the terminal field disposition of lateral geniculate neurons, whereas in adjacent visual association cortex, binding in layers III, IV, and VI faithfully followed the cortical distribution of projections from the inferior and lateral divisions of the pulvinar nucleus of the thalamus. We interpret the diffusely labeled binding sites in primate cortex as being associated with the intrinsic system of CCK-containing interneurons that are distributed throughout all layers and areas of the cortex. The stratified binding sites, however, appear to be associated with specific extrinsic peptidergic projections.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
13.
Two-dimensional HOHAHA and ROESY nuclear magnetic resonance techniques are used to obtain complete proton resonance assignments and to perform a conformational investigation of the neuropeptide neurotensin (pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu) in aqueous solution, methanol, and membrane-mimetic [deuterated sodium dodecylsulfate (SDS)] environments. Results suggest the absence of discernible elements of secondary structure in water and methanol. ROESY spectra confirm that Lys-Pro and Arg-Pro peptide bonds are all-trans, but that a significant population of cis Arg-Pro bonds arises in aqueous solution, which increases in the environment of SDS micelles. The conformational ensemble of the peptide is observed to narrow as it becomes bound through its cationic mid-region to SDS micelles, with the accompanying advent of local extended structure. The overall results indicate the inherent conformational flexibility of neurotensin, and emphasize the environmental dependence of conformation in peptides of medium length. 相似文献
14.
F. W. BACH 《Acta anaesthesiologica Scandinavica》1997,41(1):133-140
We have known the endogenous opioid peptide β-endorphin for 20 years. Surprisingly, our knowledge of the physiological role of this peptide and its receptors in modulation of pain perception is still fragmentary. Whereas most studies have tried to elucidate the physiological role of β-endorphin by reversing evoked responses by the opioid antagonist naloxone, this review focuses on quantification of release of β-endorphin in the brain as the approach to define physiological and pathophysiological roles of β-endorphin in relation to nociception. Using a lateral ventricle-cisterna magna perfusion model in the anesthetized rat, it was shown that depolarization of neurons in the arcuate nucleus of the hypothalamus, where β-endorphin is produced, was followed by release of β-endorphin to the cerebrospinal fluid compartment. Intense activation of spinal nociceptive pathways by intrathecal capsaicin injections also led to β-endorphin release. It is concluded that there may still be good reason to quantify β-endorphin in human cerebrospinal fluid to elucidate the role of β-endorphin in pain perception. 相似文献
15.
16.
本文观察了15例慢性肾功能衰竭病人透析前后的血浆心钠素浓度改变.患者透析前血浆心钠素浓度较正常人明显增高(P相似文献
17.
LARBI EL-MASDOURI ANDR AUBRY GUY BOUSSARD MICHEL MARRAUD 《Chemical biology & drug design》1992,40(6):482-486
The similar conformations and interaction modes of Ac-DL-Leu-Nme2 and Ac-Δ-Leu-NMe2 molecules in the solid state allow the comparison of their geometrical parameters. The most evident variations are essentially restricted to the α,β-unsaturated side-chain which adopts the Z-disposition. The dimensions of the peptide backbone are much less sensitive to α,β-unsaturation, with a small shortening by 0.04 Å and 0.02 Å of the N-Cα and Cα-C′ bonds, respectively, and an increase by 6° of the N-Cα- C′ bond angle. The ethylenic and amide groups in the Δ-Leu derivative are far from coplanarity, and a significant electronic conjugation of the π-orbital is likely to be rejected. 相似文献
18.
SEVERO SALVADORI REMO GUERRINI PIERO ANDREA BOREA ROBERTO TOMATIS 《Chemical biology & drug design》1992,40(5):437-444
The synthesis of pseudotetrapeptides H-Tyr-D-Ala-Phe-NH-(CH2)2-NH2 (1a), H-Tyr-D-Ala-Phe-ψ(CH2-NH)-Gly-NH2 (2a), H-Tyr-D-Ala-ψ(CH2-NH)-Phe-Gly-NH2 (3a), and H-Tyr-ψ(CH2-NH)-D-Ala-Phe-Gly-NH2 (4a), representing the N-terminal tetrapeptide sequence of dermorphin, in which amide bonds are replaced by CH2-NH bond, is described. N-acetyl-Tyr and desamino-Tyr pseudopeptide analogs (1-4b), (1-3c) are also described. The analogs were assayed in binding studies based on displacement of μ and δ-receptor selective radiolabels from rat brain membrane and in a bioassay using guinea pig ileum (GPI). Pseudopeptides in which the C-terminal (1a) or D-Ala-Phe (3a) amide bond are substituted, exhibit higher μ-affinities and μ-receptor selectivity than the corresponding Phe-Gly or Tyr-D-Ala analogs (2a, 4a). Acetyl-and desamino-Tyr pseudopeptide analogs (1-4b) and (1-3c) did not exhibit μ and δ-opioid receptor affinity at nM concentration. The relevance of the single peptide replacement and of its association to acetylation or amino group elimination of Tyr, is discussed on the basis of a receptor model for μ and δ opioids. 相似文献
19.
20.
The peptide Leu-Asp-Asp-Ser-Lys-Arg-Val-Ala-Lys-Arg-Lys-Leu-Ile-Glu, which corresponds to sequence 124 to 137 of c-erb-A protein, was synthesized and tested as substrate for protein kinase C (PKC). Although a typical recognition sequence for PKC, consisting of a cluster of basic residues, is found on the C-terminus side of serine, its phosphorylation was totally prevented by the presence of the two acidic residues on the amino-terminus side. Three analogs in which aspartyl residues were successively replaced with alanine were studied and the influence of the acidic side chain in modulating phosphorylation by PKC was thus possible to determine. The results show that the presence of a single aspartyl residue located in positions i-1 or i-2 with respect to the phosphorylable residue can almost totally abolish the positive effect of a highly favorable cluster of basic residues. These observations highlight the role of negative substrate specificity determinants in settling the protein substrate profile of protein kinase C. 相似文献