Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	AgamOBP1-Directed Discovery of Repellents to Control the Spread of Mosquito-Borne Diseases
Δημιουργός/Συγγραφέας:	Chazapi, Evanthia Kritsi, Eftichia Potamitis, Constantinos Liggri, Panagiota G V [EL] Τσιτσάνου, Αικατερίνη Drakou, Christina E Michaelakis, Antonios Papachristos, Dimitrios P [EL] Ζωγράφος, Σπύρος Ε.[EN] Zographos, Spyros E. [EL] Ζερβού, Μαρία[EN] Zervou, Maria [EL] Καλογεροπούλου, Θεοδώρα[EN] Calogeropoulou, Theodora
Ημερομηνία:	2025-09-21
Γλώσσα:	Αγγλικά
ISSN:	1860-7179 1860-7187
DOI:	10.1002/cmdc.202500555
Άλλο:	40976607
Περίληψη:	Toward the discovery of novel efficient repellents, protein-directed dynamic combinatorial chemistry (pdDCC) coupled to saturation-transfer difference (STD) NMR spectroscopy was initially employed to identify modulators of the malaria vector Anopheles gambiae Odorant Binding Protein 1 (AgamOBP1). A library of potential binders of AgamOBP1 (secondary amines) generated from two amines and seven aldehydes was designed aiming to enable interactions with critical amino acids at the DEET-site and to bridge the DEET- and Icaridin sIC-binding pockets, both implicated in repellents recognition. Solubility issues hindered the clear identification of binders among the DCL members, except for one sublibrary, leading us to shift our strategy towards the synthesis of the designed amines, followed by direct evaluation of their binding to AgamOBP1 using 1H STD NMR spectroscopy. The identified binders were further validated in vitro by fluorescence competition assays, and the most potent compounds which also possessed suitable vapor pressure were evaluated as repellents in arm-in-cage behavioral assays against Aedes albopictus. Amines 2A, 3A, 4A, and 6A showed significant repellent activity. The most potent was compound 4A (4-methyl-N-(pyridin-4-ylmethyl)aniline) which acted as a a DEET-like repellent at 0.4 μL cm- 2 dose. Thus, our strategy showcased a promising scaffold for further optimization toward efficient mosquito repellents.
Τίτλος πηγής δημοσίευσης:	ChemMedChem
Θεματική Κατηγορία:	[EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry [EL] Φασματοσκοπία[EN] Spectroscopy [EL] Βιοτεχνολογία[EN] Biotechnology [EL] Δομική Βιολογία[EN] Structural Biology [EL] Βιοχημεία[EN] Biochemistry
Λέξεις-Κλειδιά:	1H STD NMR spectroscopy Anopheles gambiae odorant binding protein 1 amines dynamic combinatorial chemistry mosquito repellent
Χρηματοδότης:	European Regional Development Fund European Social Fund (ESF) National Resources
Χρηματοδοτικό πρόγραμμα:	OPENSCREEN-GR: AnOpen-Access Research Infrastructure of Chemical Biology andTarget-Based Screening Technologies for Human and AnimalHealth Agriculture and the Environment Competitiveness, Entrepreneurship and Innovation INSPIRED-The National Research Infrastructures on Integrated Structural Biology, Drug Screening Efforts and Drug target functional characterization
Αναγνωριστικό χρηματοδοτικού προγράμματος:	MIS 5002691 QFytoTera T1EDK-0099 MIS 5000432 MIS 5002550
Κάτοχος πνευματικών δικαιωμάτων:	© 2025 The Author(s). ChemMedChem published by Wiley-VCH GmbH
Όροι και προϋποθέσεις δικαιωμάτων:	This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.1002/cmdc.202500555
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο