Replacement of His23 by Cys in a zinc finger of HIV-1 NCp7 led to a change in 1H NMR-derived 3D structure and to a loss of biological activity

AbstractThe nucleocapsid protein NCp7 of human immunodeficiency virus type 1 (HIV-1), which is necessary for the formation of infectious virions, contains two zinc fingers of the Cys-X2-Cys-X4-His-X4-Cys form. To elucidate the importance of this particular motif, well conserved in retroviruses and retroelements, we substituted the histidine residue by a cysteine in the first zinc binding domain 13VKCFNCGKEGHTARNCRA30. The structures of the mutated and native zinc complexed peptides were studied by two-dimensional 600 MHz 1H nuclear magnetic resonance (NMR) in aqueous solution. The nuclear Overhauser effects were used as constraints to determine the solution structures using DIANA software followed by AMBER energy refinement. The results show that native and mutant peptides fold into non-identical three-dimensional structures, probably accounting for the loss of retrovirus infectivity following the His-Cys point mutation

Evidence for a high-affinity uptake system for cholecystokinin octapeptide (CCK8) in rat cortical synaptosomes

Given the high resistance of the cholecystokinin octapeptide (CCK8) to in vivo peptidase degradation, the possible existence of a reuptake system for this peptide was investigated. Efficient accumulation of intact, tritiated propionyl CCK8 ([3H]pCCK8) was observed following its incubation with rat cortical synaptosomes but not with cerebellar synaptosomes, where no cholecystokinin immunoreactivity was found. This uptake process appeared to be dependent on temperature, duration of incubation, concentration of radioligand, the presence of glucose and the integrity of the synaptosomes. A Lineweaver-Burk analysis indicated that the putative uptake process is characterized by a single Km value of 10.7 nM and a Vmax of 8.5 fmol/min/mg of protein. Carbonyl cyanide-m-chlorophenyl hydrazone, an uncoupler of oxidative phosphorylation, blocked accumulation of [3H]pCCK8, whereas ouabain did not. The uptake was found to be highly specific since, among all the cholecystokinin analogues tested, only CCK8 and, to a lesser extent, CCK7, were able to inhibit [3H]pCCK8 uptake. The rate of [3H]pCCK8 uptake was not affected by CCK4, CCK5, D-Trp CCK8, BC 264, a potent and radioactivity was observed using [3H]pBC 264, a result which is not in favour of a cholecystokinin receptor-induced internalization mechanism. The potent and selective uptake mechanism characterized in this study could participate, in conjunction with extra and intracellular degradation of CCK8 by peptidases, in the interruption of cholecystokinin-conveyed messages in the brain

Antinociception induced by exogenous and endogenous opioids: Role of different brain structures

International audienc

Isis cumulative bibliography 1966-1975, a bibliography of the history of science formed from Isis critical bibliographies 91-100 indexing literature published from 1965 through 1974, edited by John Neu, II, Subjects, periods and civilizations. London, New York : Mansell, History of science society, 1985. in-4°, VII-711 pages.

Poulle Emmanuel. Isis cumulative bibliography 1966-1975, a bibliography of the history of science formed from Isis critical bibliographies 91-100 indexing literature published from 1965 through 1974, edited by John Neu, II, Subjects, periods and civilizations. London, New York : Mansell, History of science society, 1985. in-4°, VII-711 pages.. In: Bibliothèque de l'école des chartes. 1985, tome 143, livraison 2. p. 475

Generation of monoclonal antibodies specifically directed against the proximal zinc finger of HIV type 1 NCp7

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Neuroleptic-like properties of cholecystokinin analogs: Distinctive mechanisms underlying similar behavioral profiles depending on the route of administration

Rats were trained to discriminate vehicle injections from intraperitoneal injections of 3 μg/kg caerulein, a cholecystokinin (CCK) neuropeptide analog. The reward that reinforced correct choices was an electrical brain stimulation self-administered by bar pressing. Dose-response quantitative generalization was obtained by using 1 and 2 μg/kg caerulein. Qualitative generalization to the vehicle occurred after injecting 10, 20 and 200 μg/kg unsulfated CCK-8, 10, 20 and 200 μg/kg CCK-4, 5 μg/kg CCK-8 and 1 μg/kg caerulein, neurotensin or bombesin and 200 μg/kg apomorphine or 320 μg/kg amphetamine. Total generalization to the caerulein cue was obtained with 20 μg/kg sulfated CCK-8 or gastrin 2-17, 25 μg/kg somatostatin, 50 μg/kg haloperidol and 2 mg/kg chlorpromazine. The previous 5 mg/kg injection of an antiemetic drug such as chlorhydrate of trimethobenzamide did not eliminate the discriminative properties of a subsequent injection of caerulein. Our data thus tend to show that IP injection of caerulein produces effects similar to those of IP neuroleptics. © 1988.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Pierre Bernus. Histoire de l'Ile-de-France. Paris, Boivin, 1934. (Les Vieilles provinces de France.)

Cordey Jean. Pierre Bernus. Histoire de l'Ile-de-France. Paris, Boivin, 1934. (Les Vieilles provinces de France.). In: Bibliothèque de l'école des chartes. 1934, tome 95. pp. 161-162