Discovery of pan-VEGF inhibitory peptides directed to the extracellular ligand-binding domains of the VEGF receptors

Michaloski, Jussara S.; Redondo, Alexandre R.; Magalhães, Leila S.; Cambui, Caio C.; Giordano, Ricardo J.

doi:10.1126/sciadv.1600611

Cited by 27 publications

(28 citation statements)

References 57 publications

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“…1B). A cyclic CX8C (X8, any eight residues; C, cysteine) phage library displaying ∼10 10 unique sequences (19,20) was administered i.v. into a single mouse (round I of selection), and, after 30 min of systemic circulation, phage particles bound to blood vessels in different brain regions (cerebellum, olfactory bulb, and hemispheres)…”

Section: Resultsmentioning

confidence: 99%

“…Phage Library Construction. The cyclic phage display (CX8C) library used in the study was built as previously described (20). For details, see SI Appendix, SI Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

“…Phage Sequencing. Sanger sequencing was performed at the sequencing facility at the Institute of Chemistry, University of São Paulo, as previously described (20,25). High-throughput DNA sequencing was performed using the MiSeq Reagent Kit v2 (500 cycles) on an Illumina MiSeq equipment at the Center for Advanced Technologies in Genomics at Institute of Chemistry, University of São Paulo.…”

Section: Methodsmentioning

confidence: 99%

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A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina

Tang

Staquicini

Teixeira

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Endothelial heterogeneity has important implications in health and disease. Molecular markers selectively expressed in the vasculature of different organs and tissues are currently being explored in targeted therapies with promising results in preclinical and clinical studies. Noteworthy is the role that combinatorial approaches such as phage display have had in identifying such markers by using phage as nanoparticles and surrogates for billions of different peptides, screening noninvasively the vascular lumen for binding sites. Here, we show that a new peptide motif that emerged from such combinatorial screening of the vasculature binds selectively to blood vessels in the brain in vivo but not to vessels in other organs. Peptides containing a conserved motif in which amino acids Phenylalanine−Arginine−Tryptophan (FRW) predominate could be visualized by transmission electron microscopy bound to the junctions between endothelial cells in all areas of the brain, including the optic nerve, but not in other barrier-containing tissues, such as intestines and testis. Remarkably, peptides containing the motif do not bind to vessels in the retina, implying an important molecular difference between these two vascular barriers. Furthermore, the peptide allows for in vivo imaging, demonstrating that new tools for studying and imaging the brain are likely to emerge from this motif.

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Section: Resultsmentioning

confidence: 99%

“…Phage Library Construction. The cyclic phage display (CX8C) library used in the study was built as previously described (20). For details, see SI Appendix, SI Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina

Tang

Staquicini

Teixeira

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…A well-established mouse model of oxygen-induced retinopathy was performed as reported [25,26]. Briefly, litters of newborn C57BL/6 mice on postnatal day 7 and their mothers were placed in an airtight incubator and exposed to an atmosphere of 75% O 2 (hyperoxia) for 5 days.…”

Section: Oxygen-induced Retinopathy (Oir) Model Analysismentioning

confidence: 99%

“…Images were obtained on a fluorescence zoom microscope Axio Zoom V16 (Zeiss). Quantitation of angiogenic vessels was made in Adobe Photoshop as described [25,26]. Briefly, using the polygonal lasso tool, the entire retina was selected and the total number of pixels was obtained in the histogram.…”

Section: Oxygen-induced Retinopathy (Oir) Model Analysismentioning

confidence: 99%

IKKβ targeting reduces KRAS-induced lung cancer angiogenesis in vitro and in vivo: A potential anti-angiogenic therapeutic target

et al. 2019

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Objectives: The ability of tumor cells to drive angiogenesis is an important cancer hallmark that positively correlates with metastatic potential and poor prognosis. Therefore, targeting angiogenesis is a rational therapeutic approach and dissecting proangiogenic pathways is important, particularly for malignancies driven by oncogenic KRAS, which are widespread and lack effective targeted therapies. Based on published studies showing that oncogenic RAS promotes angiogenesis by upregulating the proangiogenic NF-κB target genes IL-8 and VEGF, that NF-κB activation by KRAS requires the IKKβ kinase, and that targeting IKKβ reduces KRAS-induced lung tumor growth in vivo, but has limited effects on cell growth in vitro, we hypothesized that IKKβ targeting would reduce lung tumor growth by inhibiting KRAS-induced angiogenesis. Materials and Methods: To test this hypothesis, we targeted IKKβ in KRAS-mutant lung cancer cell lines either by siRNA-mediated transfection or by treatment with Compound A (CmpdA), a highly specific IKKβ inhibitor, and used in vitro and in vivo assays to evaluate angiogenesis.

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Protocols for Building and Producing High Diversity Peptide Phage Display Libraries

Giordano,

Alecrim

2024

Methods in Molecular Biology

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Discovery of pan-VEGF inhibitory peptides directed to the extracellular ligand-binding domains of the VEGF receptors

Abstract: Extracellular ligand-binding inhibitors of receptor tyrosine kinases (eTKIs) in angiogenesis.

Cited by 27 publications

References 57 publications

A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina

A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina

IKKβ targeting reduces KRAS-induced lung cancer angiogenesis in vitro and in vivo: A potential anti-angiogenic therapeutic target

Protocols for Building and Producing High Diversity Peptide Phage Display Libraries

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