Biological evaluation and molecular docking studies of AA3052, a compound containing a Î¼-selective opioid peptide agonist DALDA and D-Phe-Phe-D-Phe-Leu-Leu-NH2, a substance P analogue (NDA@SZTAKI, Nemzeti Digitális Adattár, National Digital Data Archive)

Biological evaluation and molecular docking studies of AA3052, a compound containing a Î¼-selective opioid peptide agonist DALDA and D-Phe-Phe-D-Phe-Leu-Leu-NH2, a substance P analogue

Metaadatok

Tartalom:	http://real.mtak.hu/41286/
Archívum:	MTA Könyvtár
Gyûjtemény:	Status = Published Type = Article
Cím:	Biological evaluation and molecular docking studies of AA3052, a compound containing a Î¼-selective opioid peptide agonist DALDA and D-Phe-Phe-D-Phe-Leu-Leu-NH2, a substance P analogue
Létrehozó:	Kowalczyk, Agnieszka Kleczkowska, Patrycja RÄ™kawek, Monika Kulik, Kamila Lesniak, Anna Erdei, Anna Borics, Attila Martin, Charlotte Pawlik, Karolina Lipkowski, Andrzej W. Benyhe, SÃ¡ndor Makulska-Nowak, Helena Ballet, Steven Bujalska-Zadrozny, Magdalena
Kiadó:	Elsevier
Dátum:	2016-07-14
Téma:	QD Chemistry / kÃ©mia QD04 Organic chemistry / szerves kÃ©mia QH3011 Biochemistry / biokÃ©mia QH3015 Molecular biology / molekulÃ¡ris biolÃ³gia RM Therapeutics. Pharmacology / terÃ¡pia, gyÃ³gyszertan
Tartalmi leírás:	The design of novel drugs for pain reliefwith improved analgesic properties and diminished side effect induction profile still remains a challenging pursuit. Tolerance is one of themost burdensomephenomena thatmay hamper ongoing opioid therapy, especially in chronic pain patients. Therefore, a promising strategy of hybridizing two pharmacophores that target distinct binding sites involved in pain modulation and transmissionwas established. Previous studies have led to the development of opioid agonist/NK1 agonist hybrids that produce sufficient analgesia and also suppress opioid-induced tolerance development. In our present investigation we assessed the antinociceptive potency of a new AA3052 chimera comprised of a potent MOR selective dermorphin derivative (DALDA) and an NK1 agonist, a stabilized substance P analogue. We have shown that AA3052 significantly prolonged responses to both mechanical and noxious thermal stimuli in rats after intracerebroventricular administration. Additionally, AA3052 did not trigger the development of tolerance in a 6-day daily injection paradigm nor did it produce any sedative effects, as assessed in the rotarod performance test. However, the antinociceptive effect of AA3052 was independent of opioid receptor stimulation by the DALDA pharmacophore as shown in the agonist-stimulated G-protein assay. Altogether the current results confirm the antinociceptive effectiveness of a novel opioid/SP hybrid agonist, AA3052, and more importantly its ability to inhibit the development of tolerance.
Nyelv:	angol
Típus:	Article PeerReviewed info:eu-repo/semantics/article
Formátum:	text
Azonosító:	http://real.mtak.hu/41286/1/KOWALCZYK2016.pdf Kowalczyk, Agnieszka and Kleczkowska, Patrycja and RÄ™kawek, Monika and Kulik, Kamila and Lesniak, Anna and Erdei, Anna and Borics, Attila and Martin, Charlotte and Pawlik, Karolina and Lipkowski, Andrzej W. and Benyhe, SÃ¡ndor and Makulska-Nowak, Helena and Ballet, Steven and Bujalska-Zadrozny, Magdalena (2016) Biological evaluation and molecular docking studies of AA3052, a compound containing a Î¼-selective opioid peptide agonist DALDA and D-Phe-Phe-D-Phe-Leu-Leu-NH2, a substance P analogue. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 93. pp. 11-20. ISSN 0928-0987
Kapcsolat:	http://real.mtak.hu/41286/ https://doi.org/10.1016/j.ejps.2016.07.009