| http://dbpedia.org/ontology/abstract
|
Biphalin is a dimeric enkephalin endogenou … Biphalin is a dimeric enkephalin endogenous peptide (Tyr-D-Ala-Gly-Phe-NH)2 composed of two tetrapeptides derived from enkephalins, connected 'tail-to-tail' by a hydrazide bridge. The presence of two distinct pharmacophores confers on biphalin a high affinity for both μ and δ opioid receptors (with an EC50 of about 1-5 nM for both μ and δ receptors), therefore it has analgesic activity.Biphalin presents a considerable antinociceptive profile. In fact, when administered intracerebroventricularly in mice, biphalin displays a potency almost 7-fold greater than that of the ultra-potent alkaloid agonist, etorphine and 7000-fold greater than morphine; biphalin and morphine were found to be equipotent after intraperitoneal administration. The extraordinary in vivo potency shown by this compound is coupled with low side-effects, in particular, to produce no dependency in chronic use. For these reasons, several efforts have been carried out in order to obtain more information about structure-activity relationship (SAR). Results clearly indicate that, at least for μ receptor binding, the presence of two pharmacophores is not necessary; Tyr1 is indispensable for analgesic activity, while replacing Phe at the position 4 and 4' with non-aromatic, but lipophilic amino acids does not greatly change the binding properties and in general 4,4' positions are found to be important to design biphalin analogues with increased potency and modified μ/δ selectivity. The hydrazide linker is not fundamental for activity or binding, and it can be conveniently substituted by different conformationally constrained cycloaliphatic diamine linkers.onstrained cycloaliphatic diamine linkers.
, La Bifalina è un peptide oppioide dimerico … La Bifalina è un peptide oppioide dimerico (Tyr-D-Ala-Gly-Phe-NH)2, costituito da due identici tetrapeptidi correlati alle encefaline e connessi da coda a coda attraverso un ponte idrazinico. La presenza di due distinti farmacofori conferisce alla Bifalina un'elevata affinità sia per i recettori oppioidi μ che per i δ (con una EC50 per i due recettori di circa 1-5 nM), mostrando quindi un'attività analgesica. La Bifalina presenta un profilo antiniocicettivo degno di nota. Infatti, in seguito a somministrazione intracerebroventricolare nei topi, la Bifalina mostra una potenza 7 volte maggiore del potente agonista oppioide etorfina e 7000 volte più alta della morfina, inoltre Bifalina e morfina si sono mostrate equipotenti in seguito a somministrazione interperitoneale. La straordinaria potenza in vivo di questo composto è accompagnata da ridotti effetti collaterali, in particolare riguardo alla comparsa di dipendenza in seguito all'assunzione prolungata. Per queste ragioni, diverse ricerche sono state compiute allo scopo di ottenere maggiori informazioni sulle relazioni struttura attività (SAR). I risultati hanno chiaramente indicato che, almeno per il legame al recettore μ, la presenza di due farmacofori non è necessaria. La Tyr1 è indispensabile per l'attività analgesica, mentre la sostituzione della Phe in 4 e 4' con amminoacidi non aromatici ma lipofili non influenza particolarmente l'affinità recettoriale; in generale la posizione 4,4' è considerata importante per la realizzazione di analoghi dotati di maggiore potenza e per modulare la selettività δ/μ. Il linker idrazinico non è fondamentale per l'attività e l'affinità, e può essere convenientemente sostituito con vari sostituenti cicloalifatici dotati di maggiore rigidità conformazionale.tati di maggiore rigidità conformazionale.
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83916-01-2
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5487663
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34096965
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6578
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Space-filling model of Biphalin
, Structural formula
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None
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46
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83916
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4589475
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56
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Biphalin molecule spacefill.png
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-N,N’-[-8,13-Dibenzyl-3,6,9,12,15,18-hexaoxo-4,7,10,11,14,17-hexaazaicosane-2,19-diyl]bis[2-amino-3-propanamide]
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10
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10
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5487663
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O=C[C@@H]Cc4ccccc4
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1
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DESSEGDLRYOPTJ-VRANXALZSA-N
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350
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http://dbpedia.org/resource/Category:Dimers_%28chemistry%29 +
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http://dbpedia.org/resource/Peptide +
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http://en.wikipedia.org/wiki/Biphalin +
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|
| rdfs:comment |
La Bifalina è un peptide oppioide dimerico … La Bifalina è un peptide oppioide dimerico (Tyr-D-Ala-Gly-Phe-NH)2, costituito da due identici tetrapeptidi correlati alle encefaline e connessi da coda a coda attraverso un ponte idrazinico. La presenza di due distinti farmacofori conferisce alla Bifalina un'elevata affinità sia per i recettori oppioidi μ che per i δ (con una EC50 per i due recettori di circa 1-5 nM), mostrando quindi un'attività analgesica. La Bifalina presenta un profilo antiniocicettivo degno di nota. Infatti, in seguito a somministrazione intracerebroventricolare nei topi, la Bifalina mostra una potenza 7 volte maggiore del potente agonista oppioide etorfina e 7000 volte più alta della morfina, inoltre Bifalina e morfina si sono mostrate equipotenti in seguito a somministrazione interperitoneale. La straordinaria potene interperitoneale. La straordinaria pote
, Biphalin is a dimeric enkephalin endogenou … Biphalin is a dimeric enkephalin endogenous peptide (Tyr-D-Ala-Gly-Phe-NH)2 composed of two tetrapeptides derived from enkephalins, connected 'tail-to-tail' by a hydrazide bridge. The presence of two distinct pharmacophores confers on biphalin a high affinity for both μ and δ opioid receptors (with an EC50 of about 1-5 nM for both μ and δ receptors), therefore it has analgesic activity.Biphalin presents a considerable antinociceptive profile. In fact, when administered intracerebroventricularly in mice, biphalin displays a potency almost 7-fold greater than that of the ultra-potent alkaloid agonist, etorphine and 7000-fold greater than morphine; biphalin and morphine were found to be equipotent after intraperitoneal administration. The extraordinary in vivo potency shown by this compound iy in vivo potency shown by this compound i
|
| rdfs:label |
Bifalina
, Biphalin
|
