Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Bacterial production and direct functional screening of expanded molecular libraries for discovering inhibitors of protein aggregation
Δημιουργός/Συγγραφέας:	Delivoria D.C. Chia S. Habchi J. Perni M. Matis I. Papaevgeniou N. Reczko M. [EL] Χονδρογιάννη, Νίκη[EN] Chondrogianni, Niki Dobson C.M. Vendruscolo M. [EL] Σκρέτας, Γιώργος[EN] Skretas, George
Εκδότης:	American Association for the Advancement of Science
Ημερομηνία:	2019
Γλώσσα:	Αγγλικά
ISSN:	2375-2548
DOI:	10.1126/sciadv.aax5108
Άλλο:	PubMed ID: 31663025
Περίληψη:	Protein misfolding and aggregation are associated with a many human disorders, including Alzheimer's and Parkinson's diseases. Toward increasing the effectiveness of early-stage drug discovery for these conditions, we report a bacterial platform that enables the biosynthesis of molecular libraries with expanded diversities and their direct functional screening for discovering protein aggregation inhibitors. We illustrate this approach by performing, what is to our knowledge, the largest functional screen of small-size molecular entities described to date. We generated a combinatorial library of ~200 million drug-like, cyclic peptides and rapidly screened it for aggregation inhibitors against the amyloid- peptide (A42), linked to Alzheimer's disease. Through this procedure, we identified more than 400 macrocyclic compounds that efficiently reduce A42 aggregation and toxicity in vitro and in vivo. Finally, we applied a combination of deep sequencing and mutagenesis analyses to demonstrate how this system can rapidly determine structure-activity relationships and define consensus motifs required for bioactivity.
Τίτλος πηγής δημοσίευσης:	Science Advances
Τόμος/Κεφάλαιο:	5
Τεύχος:	10
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General)
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
EU Grant:	Horizon 2020 Framework Programme, H2020
EU Grant identifier:	819934
Κάτοχος πνευματικών δικαιωμάτων:	© 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.
Όροι και προϋποθέσεις δικαιωμάτων:	No claim to original U.S. Government Works. This is an open access article distributed under a Creative Commons Attribution License 4.0 (CC BY).
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο