Encoded libraries of chemically modified peptides

Heinis, Christian; Winter, Greg

doi:10.1016/j.cbpa.2015.02.008

Cited by 111 publications

(93 citation statements)

References 53 publications

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“…The LUMABS architecture should also allow the incorporation of more structurally constrained epitopes, such as cyclic epitopes, bicyclic epitopes or even small protein domains. [37][38][39][40] The conformational preorganization of cyclic peptides typically reduces the entropic penalty for target protein binding, and therefore these cyclic peptides bind with an increased affinity. [37][38][39] The scope of possible applications for LUMABS is very broad and includes diagnosis of infectious diseases and auto-immune diseases, monitoring the effectiveness of vaccination campaigns and quality control of biotechnological production of (bi)specific antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…[37][38][39][40] The conformational preorganization of cyclic peptides typically reduces the entropic penalty for target protein binding, and therefore these cyclic peptides bind with an increased affinity. [37][38][39] The scope of possible applications for LUMABS is very broad and includes diagnosis of infectious diseases and auto-immune diseases, monitoring the effectiveness of vaccination campaigns and quality control of biotechnological production of (bi)specific antibodies. However, we believe that LUMABS will prove particularly useful for those applications where antibody detection is presently not done, because current assay technology is too expensive, time consuming and/or technologically demanding.…”

Section: Discussionmentioning

confidence: 99%

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Detection of Antibodies in Blood Plasma Using Bioluminescent Sensor Proteins and a Smartphone

et al. 2016

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Antibody detection is of fundamental importance in many diagnostic and bioanalytical assays, yet current detection techniques tend to be laborious and/or expensive. We present a new sensor platform (LUMABS) based on bioluminescence resonance energy transfer (BRET) that allows detection of antibodies directly in solution using a smartphone as the sole piece of equipment. LUMABS are single-protein sensors that consist of the blue-light emitting luciferase NanoLuc connected via a semiflexible linker to the green fluorescent acceptor protein mNeonGreen, which are kept close together using helper domains. Binding of an antibody to epitope sequences flanking the linker disrupts the interaction between the helper domains, resulting in a large decrease in BRET efficiency. The resulting change in color of the emitted light from green-blue to blue can be detected directly in blood plasma, even at picomolar concentrations of antibody. Moreover, the modular architecture of LUMABS allows changing of target specificity by simple exchange of epitope sequences, as demonstrated here for antibodies against HIV1-p17, hemagglutinin (HA), and dengue virus type I. The combination of sensitive ratiometric bioluminescent detection and the intrinsic modularity of the LUMABS design provides an attractive generic platform for point-of-care antibody detection that avoids the complex liquid handling steps associated with conventional immunoassays.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Detection of Antibodies in Blood Plasma Using Bioluminescent Sensor Proteins and a Smartphone

et al. 2016

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“…1,2 Recently much attention has been paid to synthetic cyclic peptides designed to resemble the structure and function of their natural counterparts. 3,4 A number of strategies have been introduced for the synthesis of cyclic and bicyclic peptides, including thioether formation, 5,6 azide-alkyne click chemistry, 7,8 olefin metathesis, 9,10 KAHA ligation, 11 C-H activation stapling, 12 as well as formation of disulfide bonds and macrolactams. 13 These strategies have enabled the preparation of cyclic and bicyclic peptide libraries, screening of which has yielded an impressive array of biological probes and potential therapeutics.…”

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confidence: 99%

Iminoboronate-Based Peptide Cyclization That Responds to pH, Oxidation, and Small Molecule Modulators

2016

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As a rich source of therapeutic agents, peptide natural products usually adopt a cyclic or multicyclic scaffold that minimizes structural flexibility to favor target binding. Inspired by nature, chemists have been interested in developing synthetic cyclic and multicyclic peptides that serve as biological probes and potential therapeutics. Herein we describe a novel strategy for peptide cyclization, in which intramolecular iminoboronate formation allows spontaneous cyclization under physiologic conditions to yield monocyclic and bicyclic peptides. Importantly the iminoboronate-based cyclization can be rapidly reversed in response to multiple stimuli, including pH, oxidation and small molecules. This highly versatile strategy for peptide cyclization should find applications in many areas of chemical biology.

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“…Several complementary platform technologies have been developed over the past decade to synthesize cyclic peptide libraries of enormous structural diversity (up to 10 14 different compounds), either biologically or chemically (Figure 1). The biological methods include phage display [7,19], mRNA display [8,9,20], and peptide splicing mediated by split inteins [21,22], all of which involve ribosomal peptide synthesis. In the case of phage and mRNA display libraries, the peptides are physically linked to their encoding DNA/RNA, which can be readily sequenced to reveal the identity of a peptide ligand.…”

Section: Generating Cyclic Peptides As Ppi Inhibitorsmentioning

confidence: 99%

Targeting intracellular protein–protein interactions with cell-permeable cyclic peptides

Qian

Dougherty

Pei

2017

Current Opinion in Chemical Biology

108

109

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Intracellular protein-protein interactions (PPIs) are challenging targets for conventional drug modalities, because small molecules generally do not bind to their large, flat binding sites with high affinity, whereas monoclonal antibodies cannot cross the cell membrane to reach the targets. Cyclic peptides in the 700–2000 molecular-weight range have the sufficient size and a balanced conformational flexibility/rigidity for binding to flat PPI interfaces with antibody-like affinity and specificity. Several powerful cyclic peptide library technologies were developed over the past decade to rapidly discover potent, specific cyclic peptide ligands against proteins of interest including those involved in PPIs. Methods are also being developed to enhance the membrane permeability of cyclic peptides through both passive diffusion and active transport mechanisms. Integration of the permeability-enhancing elements into cyclic peptide design has led to an increasing number of cell-permeable and biologically active cyclic peptides against intracellular PPIs. In this account, we review the recent developments in the design and synthesis of cell-permeable cyclic peptides.

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Encoded libraries of chemically modified peptides

Cited by 111 publications

References 53 publications

Detection of Antibodies in Blood Plasma Using Bioluminescent Sensor Proteins and a Smartphone

Detection of Antibodies in Blood Plasma Using Bioluminescent Sensor Proteins and a Smartphone

Iminoboronate-Based Peptide Cyclization That Responds to pH, Oxidation, and Small Molecule Modulators

Targeting intracellular protein–protein interactions with cell-permeable cyclic peptides

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