<i>In Vitro</i> Selection of Multiple Libraries Created by Genetic Code Reprogramming To Discover Macrocyclic Peptides That Antagonize VEGFR2 Activity in Living Cells

Kawakami, Takashi; Ishizawa, Takahiro; Fujino, Tomoshige; Reid, Patrick; Suga, Hiroaki; Murakami, Hiroshi

doi:10.1021/cb300697h

Cited by 57 publications

(53 citation statements)

References 51 publications

(94 reference statements)

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“…Coupling in vitro translation methods with mRNA display, other groups have successfully isolated potent macrocyclic peptide inhibitors for a variety of other therapeutically relevant protein targets. 36–41 …”

Section: Introductionmentioning

confidence: 99%

Ribosomal Synthesis of Macrocyclic Peptides in Vitro and in Vivo Mediated by Genetically Encoded Aminothiol Unnatural Amino Acids

et al. 2015

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A versatile method for orchestrating the formation of side-chain-to-tail cyclic peptides from ribosomally derived polypeptide precursors is reported. Upon ribosomal incorporation into intein-containing precursor proteins, designer unnatural amino acids bearing side-chain 1,3- or 1,2-aminothiol functionalities are able to promote the cyclization of a downstream target peptide sequence via a C-terminal ligation/ring contraction mechanism. Using this approach, peptide macrocycles of variable size and composition could be generated in a pH-triggered manner in vitro, or directly in living bacterial cells. This methodology furnishes a new platform for the creation and screening of genetically encoded libraries of conformationally constrained peptides. This strategy was applied to identify and isolate a low micromolar streptavidin binder (KD = 1.1 µM) from a library of cyclic peptides produced in E. coli, thereby illustrating its potential toward aiding the discovery of functional peptide macrocycles.

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Section: Introductionmentioning

confidence: 99%

Ribosomal Synthesis of Macrocyclic Peptides in Vitro and in Vivo Mediated by Genetically Encoded Aminothiol Unnatural Amino Acids

et al. 2015

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“…Suga's group recently selected inhibitors of VEGFR2 from libraries produced in a PURE translation system with 16 natural amino acids and four backbone-modified unnatural amino acids (cycloleucine, D-phenylalanine, D-tyrosine, N -methyl-histidine, and N -methyl-phenyl-alanine) [90]. The most potent compound L1 is a cyclic head-to-tail thioether macrocyclic peptide, which showed relatively high serum stability and was much more potent than previously reported small molecule (“monomer”) antagonists obtained from combinatorial libraries [91-93].…”

Section: Biological Library Methodsmentioning

confidence: 99%

Tumor-targeting peptides from combinatorial libraries

Liu

Xiao

et al. 2017

Advanced Drug Delivery Reviews

162

102

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Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges infighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors.

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“…Due to its higher throughput, greater automation, and lower cost compared to other methods of affinity detection, BLI has been applied in the study of more and more molecular interactions [52–54]. BLI assays were run at 30 °C on an Octet QK using Protein A (ProA) biosensors (Pall ForteBio Corp., Menlo Park, CA) and black 96-well microplates.…”

Section: Methodsmentioning

confidence: 99%

Highly stable aptamers selected from a 2′-fully modified fGmH RNA library for targeting biomaterials

2015

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When developed as targeting ligands for the in vivo delivery of biomaterials to biological systems, RNA aptamers immediately face numerous obstacles, in particular nuclease degradation and post-selection 2′ modification. This study aims to develop a novel class of highly stable, 2′-fully modified RNA aptamers that are ideal for the targeted delivery of biomaterials. We demonstrated the facile transcription of a fGmH (2′-F-dG, 2′-OMe-dA/dC/dU) RNA library with unexpected hydrophobicity, the direct selection of aptamers from a fGmH RNA library that bind Staphylococcus aureus Protein A (SpA) as a model target, and the superior nuclease and serum stability of these aptamers compared to 2′-partially modified RNA variants. Characterizations of fGmH RNA aptamers binding to purified SpA and to endogenous SpA present on the surface of S. aureus cells demonstrate fGmH RNA aptamer selectivity and stability. Significantly, fGmH RNA aptamers were able to functionalize, stabilize, and further deliver aggregation-prone silver nanoparticles (AgNPs) to S. aureus with SpA-dependent antimicrobial effects. This study describes a novel aptamer class with considerable potential to improve the in vivo applicability of nucleic acid-based affinity molecules to biomaterials.

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In Vitro Selection of Multiple Libraries Created by Genetic Code Reprogramming To Discover Macrocyclic Peptides That Antagonize VEGFR2 Activity in Living Cells

Cited by 57 publications

References 51 publications

Ribosomal Synthesis of Macrocyclic Peptides in Vitro and in Vivo Mediated by Genetically Encoded Aminothiol Unnatural Amino Acids

Ribosomal Synthesis of Macrocyclic Peptides in Vitro and in Vivo Mediated by Genetically Encoded Aminothiol Unnatural Amino Acids

Tumor-targeting peptides from combinatorial libraries

Highly stable aptamers selected from a 2′-fully modified fGmH RNA library for targeting biomaterials

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