Εξειδίκευση τύπου :	Κεφάλαιο βιβλίου
Τίτλος:	Integrated bacterial production and functional screening of expanded cyclic peptide libraries for identifying chemical rescuers of pathogenic protein misfolding and aggregation
Δημιουργός/Συγγραφέας:	Delivoria, Dafni C. [EL] Σκρέτας, Γιώργος[EN] Skretas, George
Επιμελητής έκδοσης:	Iranzo, Olga Roque, Ana Cecília
Εκδότης:	Springer Nature
Τόπος έκδοσης:	Humana, New York
Ημερομηνία:	2020
Γλώσσα:	Αγγλικά
ISBN:	978-1-0716-0719-0 978-1-0716-0720-6
ISSN:	1949-2448 1949-2456
DOI:	10.1007/978-1-0716-0720-6_13
Περίληψη:	Protein misfolding and aggregation are defining features of a wide range of human conditions, collectively termed protein misfolding diseases. These include disorders with diverse pathologies and symptoms, such as Alzheimer’s disease, Parkinson’s disease, and type 2 diabetes, the vast majority of which impose a very high socio-economic burden on humanity and remain incurable to date. To address this unmet medical need, we report here a simple and high-throughput system for identifying macrocyclic rescuers of protein misfolding. In this system, Escherichia coli cells are genetically engineered in order to perform two simultaneous tasks: (1) produce combinatorial libraries of head-to-tail cyclic oligopeptides using protein-splicing technology and (2) enable the identification of the bioactive cyclic peptides that correct the problematic folding and/or inhibit the aggregation of disease-associated misfolding-prone proteins using a genetic assay that links the folding of the target protein to a fluorescent phenotype. In this way, the bioactive cyclic peptide hits are identified in an ultrahigh-throughput manner using flow cytometric cell sorting, thus significantly decreasing the overall cost, time, and complexity of early drug discovery for these notorious diseases.
Τίτλος πηγής δημοσίευσης:	Peptide and Protein Engineering: From Concepts to Biotechnological Applications
Σελίδες:	237–266
Σειρά δημοσίευσης:	Springer Protocols Handbooks
Θεματική Κατηγορία:	[EL] Βιοχημεία[EN] Biochemistry [EL] Μικροβιολογία[EN] Microbiology [EL] Χημική Βιολογία[EN] Chemical Biology [EL] Βιοτεχνολογία[EN] Biotechnology
Λέξεις-Κλειδιά:	Protein misfolding diseases Protein aggregation High-throughput screening SICLOPPS technology Cyclic peptides
Κάτοχος πνευματικών δικαιωμάτων:	Copyright © 2020 Springer Science+Business Media, LLC, part of Springer Nature
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://link.springer.com/protocol/10.1007/978-1-0716-0720-6_13#editor-information
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://link.springer.com/book/10.1007/978-1-0716-0720-6
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο