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Rapid discovery of cyclic peptide protein aggregation inhibitors by continuous selection
by
Andon, James S.
, Wang, Tina
, Zhang, Jingwei
, Li, Lingjun
, Yang, Linwei
in
639/638/92
/ 639/638/92/552
/ Amylin
/ Amyloid
/ Amyloid beta-Peptides - antagonists & inhibitors
/ Amyloid beta-Peptides - chemistry
/ Amyloid beta-Peptides - metabolism
/ Biochemical Engineering
/ Biochemistry
/ Bioorganic Chemistry
/ Cell Biology
/ Chemistry
/ Chemistry and Materials Science
/ Chemistry/Food Science
/ Coding
/ Directed Molecular Evolution
/ Drug Discovery - methods
/ E coli
/ Escherichia coli
/ Escherichia coli - genetics
/ Escherichia coli - metabolism
/ Genetic code
/ Humans
/ Inhibitors
/ Islet Amyloid Polypeptide - antagonists & inhibitors
/ Islet Amyloid Polypeptide - chemistry
/ Islet Amyloid Polypeptide - metabolism
/ Peptide Fragments - antagonists & inhibitors
/ Peptide Fragments - chemistry
/ Peptide Fragments - metabolism
/ Peptide inhibitors
/ Peptide libraries
/ Peptide Library
/ Peptides
/ Peptides, Cyclic - chemistry
/ Peptides, Cyclic - pharmacology
/ Polypeptides
/ Protein Aggregates - drug effects
/ Protein interaction
/ Proteins
2025
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Rapid discovery of cyclic peptide protein aggregation inhibitors by continuous selection
by
Andon, James S.
, Wang, Tina
, Zhang, Jingwei
, Li, Lingjun
, Yang, Linwei
in
639/638/92
/ 639/638/92/552
/ Amylin
/ Amyloid
/ Amyloid beta-Peptides - antagonists & inhibitors
/ Amyloid beta-Peptides - chemistry
/ Amyloid beta-Peptides - metabolism
/ Biochemical Engineering
/ Biochemistry
/ Bioorganic Chemistry
/ Cell Biology
/ Chemistry
/ Chemistry and Materials Science
/ Chemistry/Food Science
/ Coding
/ Directed Molecular Evolution
/ Drug Discovery - methods
/ E coli
/ Escherichia coli
/ Escherichia coli - genetics
/ Escherichia coli - metabolism
/ Genetic code
/ Humans
/ Inhibitors
/ Islet Amyloid Polypeptide - antagonists & inhibitors
/ Islet Amyloid Polypeptide - chemistry
/ Islet Amyloid Polypeptide - metabolism
/ Peptide Fragments - antagonists & inhibitors
/ Peptide Fragments - chemistry
/ Peptide Fragments - metabolism
/ Peptide inhibitors
/ Peptide libraries
/ Peptide Library
/ Peptides
/ Peptides, Cyclic - chemistry
/ Peptides, Cyclic - pharmacology
/ Polypeptides
/ Protein Aggregates - drug effects
/ Protein interaction
/ Proteins
2025
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Rapid discovery of cyclic peptide protein aggregation inhibitors by continuous selection
by
Andon, James S.
, Wang, Tina
, Zhang, Jingwei
, Li, Lingjun
, Yang, Linwei
in
639/638/92
/ 639/638/92/552
/ Amylin
/ Amyloid
/ Amyloid beta-Peptides - antagonists & inhibitors
/ Amyloid beta-Peptides - chemistry
/ Amyloid beta-Peptides - metabolism
/ Biochemical Engineering
/ Biochemistry
/ Bioorganic Chemistry
/ Cell Biology
/ Chemistry
/ Chemistry and Materials Science
/ Chemistry/Food Science
/ Coding
/ Directed Molecular Evolution
/ Drug Discovery - methods
/ E coli
/ Escherichia coli
/ Escherichia coli - genetics
/ Escherichia coli - metabolism
/ Genetic code
/ Humans
/ Inhibitors
/ Islet Amyloid Polypeptide - antagonists & inhibitors
/ Islet Amyloid Polypeptide - chemistry
/ Islet Amyloid Polypeptide - metabolism
/ Peptide Fragments - antagonists & inhibitors
/ Peptide Fragments - chemistry
/ Peptide Fragments - metabolism
/ Peptide inhibitors
/ Peptide libraries
/ Peptide Library
/ Peptides
/ Peptides, Cyclic - chemistry
/ Peptides, Cyclic - pharmacology
/ Polypeptides
/ Protein Aggregates - drug effects
/ Protein interaction
/ Proteins
2025
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Rapid discovery of cyclic peptide protein aggregation inhibitors by continuous selection
Journal Article
Rapid discovery of cyclic peptide protein aggregation inhibitors by continuous selection
2025
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Overview
Protein aggregates are associated with numerous diseases. Here we report a platform for the rapid phenotypic selection of protein aggregation inhibitors from genetically encoded cyclic peptide libraries in
Escherichia coli
based on phage-assisted continuous evolution (PACE). We developed a new PACE-compatible selection for protein aggregation inhibition and used it to identify cyclic peptides that suppress amyloid-β42 and human islet amyloid polypeptide aggregation. Additionally, we integrated a negative selection that removes false positives and off-target hits, greatly improving cyclic peptide selectivity. We show that selected inhibitors are active when chemically resynthesized in in vitro assays. Our platform provides a powerful approach for the rapid discovery of cyclic peptide inhibitors of protein aggregation and may serve as the basis for the future evolution of cyclic peptides with a broad spectrum of inhibitory activities.
A platform for the continuous selection of protein aggregation inhibitors from genetically encoded cyclic peptide libraries in
Escherichia coli
was developed. This platform was used to discover cyclic peptides that suppress aggregation of amyloid-β42 and human islet amyloid polypeptide.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Amylin
/ Amyloid
/ Amyloid beta-Peptides - antagonists & inhibitors
/ Amyloid beta-Peptides - chemistry
/ Amyloid beta-Peptides - metabolism
/ Chemistry and Materials Science
/ Coding
/ Directed Molecular Evolution
/ E coli
/ Escherichia coli - metabolism
/ Humans
/ Islet Amyloid Polypeptide - antagonists & inhibitors
/ Islet Amyloid Polypeptide - chemistry
/ Islet Amyloid Polypeptide - metabolism
/ Peptide Fragments - antagonists & inhibitors
/ Peptide Fragments - chemistry
/ Peptide Fragments - metabolism
/ Peptides
/ Peptides, Cyclic - chemistry
/ Peptides, Cyclic - pharmacology
/ Protein Aggregates - drug effects
/ Proteins
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