Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Structural Features Influencing the Bioactive Conformation of Angiotensin II and Angiotensin A: Relationship between Receptor Desensitization, Addiction, and the Blood-Brain Barrier
Δημιουργός/Συγγραφέας:	Moore, Graham J Ridway, Harry Gadanec, Laura Kate Apostolopoulos, Vasso Zulli, Anthony Swiderski, Jordan Kelaidonis, Konstantinos Vidali, Veroniki P Matsoukas, Minos-Timotheos [EL] Χασάπης, Χρήστος[EN] Chasapis, Christos Matsoukas, John M
Ημερομηνία:	2024-05-26
Γλώσσα:	Αγγλικά
ISSN:	1422-0067
DOI:	10.3390/ijms25115779
Άλλο:	38891966
Περίληψη:	The N-terminal portion of the octapeptide angiotensin II (DRVYIHPF; AngII), a vasopressor peptide that favorably binds to, and activates, AngII type 1 receptor (AT1R), has an important role in maintaining bioactive conformation. It involves all three charged groups, namely (i) the N-terminal amino group cation, (ii) the Asp sidechain anion and (iii) the Arg guanidino cation. Neutralization of any one of these three charged groups results in a substantial reduction (<5%) in bioactivity, implicating a specialized function for this cluster. In contrast, angiotensin A (ARVYIHPF; AngA) has reduced bioactivity at AT1R; however, replacement of Asp in AngII with sarcosine (N-methyl-glycine) not only restores bioactivity but increases the activity of agonist, antagonist, and inverse agonist analogues. A bend produced at the N-terminus by the introduction of the secondary amino acid sarcosine is thought to realign the functional groups that chaperone the C-terminal portion of AngII, allowing transfer of the negative charge originating at the C-terminus to be transferred to the Tyr hydroxyl-forming tyrosinate anion, which is required to activate the receptor and desensitizes the receptor (tachyphylaxis). Peptide (sarilesin) and nonpeptide (sartans) moieties, which are long-acting inverse agonists, appear to desensitize the receptor by a mechanism analogous to tachyphylaxis. Sartans/bisartans were found to bind to alpha adrenergic receptors resulting in structure-dependent desensitization or resensitization. These considerations have provided information on the mechanisms of receptor desensitization/tolerance and insights into possible avenues for treating addiction. In this regard sartans, which appear to cross the blood-brain barrier more readily than bisartans, are the preferred drug candidates.
Τίτλος πηγής δημοσίευσης:	International journal of molecular sciences
Τόμος/Κεφάλαιο:	25
Τεύχος:	11
Θεματική Κατηγορία:	[EL] Δομική Βιολογία[EN] Structural Biology [EL] Θεραπευτική. Φαρμακολογία[EN] Therapeutics.Pharmacology [EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry [EL] Βιοχημεία[EN] Biochemistry
Λέξεις-Κλειδιά:	G-protein coupled receptor addiction angiotensin II arginine bisartan blood–brain barrier conformation of angiotensin coronavirus disease 2019 receptor desensitization
Κάτοχος πνευματικών δικαιωμάτων:	© 2024 by the authors. Licensee MDPI, Basel, Switzerland.
Όροι και προϋποθέσεις δικαιωμάτων:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.3390/ijms25115779
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο