Extension of in vivo half-life of biologically active molecules by XTEN protein polymers

XTEN™ is a class of unstructured hydrophilic, biodegradable protein polymers designed to increase the half-lives of therapeutic peptides and proteins. XTEN polymers and XTEN fusion proteins are typically expressed in Escherichia coli and purified by conventional protein chromatography as monodispers...

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Published in	Journal of controlled release Vol. 240; pp. 52 - 66
Main Authors	Podust, Vladimir N., Balan, Sibu, Sim, Bee-Cheng, Coyle, Michael P., Ernst, Ulrich, Peters, Robert T., Schellenberger, Volker
Format	Journal Article
Language	English
Published	Netherlands Elsevier B.V 28.10.2016
Subjects	Animals biodegradability Biological Products - chemistry Biological Products - pharmacokinetics Biotherapeutics Chemical conjugation chromatography Clinical Trials as Topic - methods Drug Discovery - methods Drug Discovery - trends drugs Escherichia coli Genetic fusion Half-Life Half-life extension Humans hydrodynamics hydrophilicity Peptides polymers Polymers - chemistry Polymers - pharmacokinetics polypeptides Protein Structure, Secondary proteins Proteins - chemistry Proteins - pharmacokinetics therapeutics XTEN protein polymer XTEN protein polymer Biotherapeutics Chemical conjugation Peptides Half-life extension Genetic fusion
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Abstract	XTEN™ is a class of unstructured hydrophilic, biodegradable protein polymers designed to increase the half-lives of therapeutic peptides and proteins. XTEN polymers and XTEN fusion proteins are typically expressed in Escherichia coli and purified by conventional protein chromatography as monodisperse polypeptides of exact length and sequence. Unstructured XTEN polypeptides have hydrodynamic volumes significantly larger than typical globular proteins of similar mass, thus imparting a bulking effect to the therapeutic payloads attached to them. Since their invention, XTEN polypeptides have been utilized to extend the half-lives of a variety of peptide- and protein-based therapeutics. Multiple clinical and preclinical studies and related drug discovery and development efforts are in progress. This review details the most current understanding of physicochemical properties and biological behavior of XTEN and XTENylated molecules. Additionally, the development path and status of several advanced drug discovery and development efforts are highlighted. [Display omitted]
AbstractList	XTEN™ is a class of unstructured hydrophilic, biodegradable protein polymers designed to increase the half-lives of therapeutic peptides and proteins. XTEN polymers and XTEN fusion proteins are typically expressed in Escherichia coli and purified by conventional protein chromatography as monodisperse polypeptides of exact length and sequence. Unstructured XTEN polypeptides have hydrodynamic volumes significantly larger than typical globular proteins of similar mass, thus imparting a bulking effect to the therapeutic payloads attached to them. Since their invention, XTEN polypeptides have been utilized to extend the half-lives of a variety of peptide- and protein-based therapeutics. Multiple clinical and preclinical studies and related drug discovery and development efforts are in progress. This review details the most current understanding of physicochemical properties and biological behavior of XTEN and XTENylated molecules. Additionally, the development path and status of several advanced drug discovery and development efforts are highlighted. [Display omitted] XTEN™ is a class of unstructured hydrophilic, biodegradable protein polymers designed to increase the half-lives of therapeutic peptides and proteins. XTEN polymers and XTEN fusion proteins are typically expressed in Escherichia coli and purified by conventional protein chromatography as monodisperse polypeptides of exact length and sequence. Unstructured XTEN polypeptides have hydrodynamic volumes significantly larger than typical globular proteins of similar mass, thus imparting a bulking effect to the therapeutic payloads attached to them. Since their invention, XTEN polypeptides have been utilized to extend the half-lives of a variety of peptide- and protein-based therapeutics. Multiple clinical and preclinical studies and related drug discovery and development efforts are in progress. This review details the most current understanding of physicochemical properties and biological behavior of XTEN and XTENylated molecules. Additionally, the development path and status of several advanced drug discovery and development efforts are highlighted.XTEN™ is a class of unstructured hydrophilic, biodegradable protein polymers designed to increase the half-lives of therapeutic peptides and proteins. XTEN polymers and XTEN fusion proteins are typically expressed in Escherichia coli and purified by conventional protein chromatography as monodisperse polypeptides of exact length and sequence. Unstructured XTEN polypeptides have hydrodynamic volumes significantly larger than typical globular proteins of similar mass, thus imparting a bulking effect to the therapeutic payloads attached to them. Since their invention, XTEN polypeptides have been utilized to extend the half-lives of a variety of peptide- and protein-based therapeutics. Multiple clinical and preclinical studies and related drug discovery and development efforts are in progress. This review details the most current understanding of physicochemical properties and biological behavior of XTEN and XTENylated molecules. Additionally, the development path and status of several advanced drug discovery and development efforts are highlighted. XTEN™ is a class of unstructured hydrophilic, biodegradable protein polymers designed to increase the half-lives of therapeutic peptides and proteins. XTEN polymers and XTEN fusion proteins are typically expressed in Escherichia coli and purified by conventional protein chromatography as monodisperse polypeptides of exact length and sequence. Unstructured XTEN polypeptides have hydrodynamic volumes significantly larger than typical globular proteins of similar mass, thus imparting a bulking effect to the therapeutic payloads attached to them. Since their invention, XTEN polypeptides have been utilized to extend the half-lives of a variety of peptide- and protein-based therapeutics. Multiple clinical and preclinical studies and related drug discovery and development efforts are in progress. This review details the most current understanding of physicochemical properties and biological behavior of XTEN and XTENylated molecules. Additionally, the development path and status of several advanced drug discovery and development efforts are highlighted.
Author	Balan, Sibu Sim, Bee-Cheng Ernst, Ulrich Coyle, Michael P. Podust, Vladimir N. Peters, Robert T. Schellenberger, Volker
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Keywords	XTEN protein polymer Biotherapeutics Chemical conjugation Peptides Half-life extension Genetic fusion
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Snippet	XTEN™ is a class of unstructured hydrophilic, biodegradable protein polymers designed to increase the half-lives of therapeutic peptides and proteins. XTEN...
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SubjectTerms	Animals biodegradability Biological Products - chemistry Biological Products - pharmacokinetics Biotherapeutics Chemical conjugation chromatography Clinical Trials as Topic - methods Drug Discovery - methods Drug Discovery - trends drugs Escherichia coli Genetic fusion Half-Life Half-life extension Humans hydrodynamics hydrophilicity Peptides polymers Polymers - chemistry Polymers - pharmacokinetics polypeptides Protein Structure, Secondary proteins Proteins - chemistry Proteins - pharmacokinetics therapeutics XTEN protein polymer
Title	Extension of in vivo half-life of biologically active molecules by XTEN protein polymers
URI	https://dx.doi.org/10.1016/j.jconrel.2015.10.038 https://www.ncbi.nlm.nih.gov/pubmed/26497931 https://www.proquest.com/docview/1826648729 https://www.proquest.com/docview/2000257035
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