Peptide Aptamers: Development and Applications

Reverdatto, Sergey; Burz, David S.; Shekhtman, Alexander

doi:10.2174/1568026615666150413153143

Cited by 149 publications

(116 citation statements)

References 233 publications

(304 reference statements)

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“…Interest in chemical modifications that enable the translocation of peptides into cells is spurred on by the increasing use of biologics, peptides, proteins and their mimetics as tools in research and therapeutic development 1–3 . Several different covalent linkages have been used to stabilize the receptor bound helical conformations of peptides in solution 4 .…”

Section: Introductionmentioning

confidence: 99%

Enhancing Specific Disruption of Intracellular Protein Complexes by Hydrocarbon Stapled Peptides Using Lipid Based Delivery

Thean

Ebo

Luxton

et al. 2017

Sci Rep

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Linear peptides can mimic and disrupt protein-protein interactions involved in critical cell signaling pathways. Such peptides however are usually protease sensitive and unable to engage with intracellular targets due to lack of membrane permeability. Peptide stapling has been proposed to circumvent these limitations but recent data has suggested that this method does not universally solve the problem of cell entry and can lead to molecules with off target cell lytic properties. To address these issues a library of stapled peptides was synthesized and screened to identify compounds that bound Mdm2 and activated cellular p53. A lead peptide was identified that activated intracellular p53 with negligible nonspecific cytotoxicity, however it still bound serum avidly and only showed a marginal improvement in cellular potency. These hurdles were overcome by successfully identifying a pyridinium-based cationic lipid formulation, which significantly improved the activity of the stapled peptide in a p53 reporter cell line, principally through increased vesicular escape. These studies underscore that stapled peptides, which are cell permeable and target specific, can be identified with rigorous experimental design and that these properties can be improved through use with lipid based formulations. This work should facilitate the clinical translation of stapled peptides.

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Section: Introductionmentioning

confidence: 99%

Enhancing Specific Disruption of Intracellular Protein Complexes by Hydrocarbon Stapled Peptides Using Lipid Based Delivery

Thean

Ebo

Luxton

et al. 2017

Sci Rep

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“…We speculate that combining the switches presented here with engineered peptides or proteins [104] that bind with high specificity and affinity their targets is a promising strategy in this direction.…”

Section: Discussionmentioning

confidence: 99%

Go in! Go out! Inducible control of nuclear localization

Ventura

Kuhlman

2016

Current Opinion in Chemical Biology

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Cells have evolved a variety of mechanisms to regulate the enormous complexity of processes taking place inside them. One mechanism consists in tightly controlling the localization of macromolecules, keeping them away from their place of action until needed. Since a large fraction of the cellular response to external stimuli is mediated by gene expression, it is not surprising that transcriptional regulators are often subject to stimulus-induced nuclear import or export. Here we review recent methods in chemical biology and optogenetics for controlling the nuclear localization of proteins of interest inside living cells. These methods allow researchers to regulate protein activity with exquisite spatiotemporal control, and open up new possibilities for studying the roles of proteins in a broad array of cellular processes and biological functions.

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“…Currently, scaffolds that function in a manner analogous to immunoglobulin CDR are considered appropriate for creating a peptide aptamer library 12. Peptide aptamers provide a powerful alternative approach to target the peptide-protein interaction (PPI) interface 13.…”

Section: Introductionmentioning

confidence: 99%

“…Typically, peptide aptamers are defined as affinity binders consisting of short (5-20) aa residues stretching from variable peptide regions constrained within a protein scaffold 12. In this study, we propose to use a known epitope (KPNDAINF) derived from H5N1 HA 10 as a detection agent.…”

Section: Introductionmentioning

confidence: 99%

Rapid Detection of Avian Influenza Virus by Fluorescent Diagnostic Assay using an Epitope-Derived Peptide

et al. 2017

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Currently, the point of care testing (POCT) is not fully developed for subtype-specific avian influenza virus detection. In this study, an H5N1 hemaglutinin 1 (HA1) epitope (P0: KPNDAINF) and three modified peptides (P1: KPNTAINF, P2: KPNGAINF, P3: KPNDAINDAINF) were evaluated as POCT elements for rapid detection of avian influenza virus. Based on modeling predictions by Autodock Vina, binding affinity varied depending on alteration of one amino acid in these peptides. The binding energy of P2 indicated its potential for a strong interaction with HA. Fluorescence-linked immunosorbent assay experimentally demonstrated the interaction between these peptides and virus. The four peptides interacted with HA1 of H5N3 with different binding affinities with P2 showing the strongest binding affinity. When P0 and P2 peptides were used in rapid fluorescent immunochromatographic test (FICT) as detection elements, the inter-assay coefficients of variation (CV) indicated that P2-linked FICT was more acceptable than the P0-linked FICT in the presence of human specimens. Antibody pair-linked FICT was influenced by clinical samples more than the P2-linked FICT assay, which showed a 4-fold improvement in the detection limit of H5N3 and maintained H5 subtype-specificity. Compared to the rapid diagnostic test (RDT) which is not specific for influenza subtypes, P2-linked FICT could increase virus detection. In conclusion, results of this study suggest that HA epitope-derived peptides can be used as alternatives to antibodies for a rapid fluorescent diagnostic assay to detect avian influenza virus.

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Peptide Aptamers: Development and Applications

Cited by 149 publications

References 233 publications

Enhancing Specific Disruption of Intracellular Protein Complexes by Hydrocarbon Stapled Peptides Using Lipid Based Delivery

Enhancing Specific Disruption of Intracellular Protein Complexes by Hydrocarbon Stapled Peptides Using Lipid Based Delivery

Go in! Go out! Inducible control of nuclear localization

Rapid Detection of Avian Influenza Virus by Fluorescent Diagnostic Assay using an Epitope-Derived Peptide

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