Identification of Amino Acid Residues in PEPHC1 Important for Binding to the Tumor‐Specific Receptor EGFRvIII

Hansen, Casper Worm; Pb, Hansen; Pedersen, Nina Marie; Poulsen, Hans Skovgaard; Gillings, Nic; Kjær, Andreas

doi:10.1111/j.1747-0285.2008.00706.x

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…As previously mentioned, we have reported an alanine scan of PEPHC1 to identify the amino acid residues important for binding to EGFRvIII 17. Our results indicated that the amino acid residues at the N‐terminus of PEPHC1 are essential for the binding to the mutated receptor.…”

Section: Resultssupporting

confidence: 57%

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Identification of novel peptide ligands for the cancer‐specific receptor mutation EFGRvIII using a mixture‐based synthetic combinatorial library

Denholt

Pedersen

et al. 2008

Biopolymers

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We report here, the design and synthesis of a positional scanning synthetic combinatorial library for the identification of novel peptide ligands targeted against the cancer-specific epidermal growth factor tyrosine kinase receptor mutation variant III (EGFRvIII). This receptor is expressed in several kinds of cancer, in particular, ovarian, glioblastomas, and breast cancer, but not in normal tissue. The library consisted of six individual positional sublibraries in the format, H-O(1-6)XXXXX-NH(2), O being one of the 19 proteinogenic amino acids (cysteine omitted) and X an equimolar mixture of these. The library consisted of 114 mixtures in total. Using a biotin-streptavidin assay, the binding of each sublibrary to NR6M, NR6W-A, and NR6 cells was tested. These cells express EGFRvIII, EGFR, and neither of the receptors, respectively. The result from each sublibrary was examined to identify the most active amino acid residue at each position. On the basis of this knowledge, eight peptides were synthesized and tested for binding to EGFRvIII. We identified one peptide, H-FALGEA-NH(2), that showed more selective binding to the mutated receptor than the EGFRvIII specific peptide PEPHC1. This study demonstrates the value of using mixture-based combinatorial positional scanning libraries for the identification of novel peptide ligands targeted against the cancer-specific EGFRvIII. Our best candidate H-FALGEA-NH(2) will be radioactively labeled and evaluated as an imaging agent for positron emission tomography investigation for diagnosis, staging, and monitoring of therapy of various types of cancer.

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Section: Resultssupporting

confidence: 57%

“…PEPHC1 had binding ability and selectivity to EGFRvIII. Very recently, we identified the amino acid residues in PEPHC1 important for binding to the tumor‐specific receptor EGFRvIII 17. Our results indicated that the amino acid residues at the N‐terminus of PEPHC1 are essential for the binding to the mutated receptor.…”

Section: Introductionmentioning

confidence: 78%

Identification of novel peptide ligands for the cancer‐specific receptor mutation EFGRvIII using a mixture‐based synthetic combinatorial library

Denholt

Pedersen

et al. 2008

Biopolymers

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“…Thus, EGFRvIII is a promising marker for sensitive glioblastoma detection and localization in molecular MR imaging. PEPHC1 (the sequence: HFLIIGFMRRAACGA) is a small peptide that has been identified for specific binding with EGFRvIII [26]. Thus PEPHC1 grafting to PEGylated SPIONs could help to construct a targeted nanoprobe for sensitive characterization and detection of glioblastoma.…”

Section: Introductionmentioning

confidence: 99%

Engineered superparamagnetic iron oxide nanoparticles (SPIONs) for dual-modality imaging of intracranial glioblastoma via EGFRvIII targeting

Liu¹,

Du²,

Li³

et al. 2019

Beilstein J. Nanotechnol.

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In this work, a peptide-modified, biodegradable, nontoxic, brain-tumor-targeting nanoprobe based on superparamagnetic iron oxide nanoparticles (SPIONs) (which have been commonly used as T 2-weighted magnetic resonance (MR) contrast agents) was successfully synthesized and applied for accurate molecular MR imaging and sensitive optical imaging. PEPHC1, a short peptide which can specifically bind to epidermal growth factor receptor variant III (EGFRvIII) that is overexpressed in glioblastoma, was conjugated with SPIONs to construct the nanoprobe. Both in vitro and in vivo MR and optical imaging demonstrated that the as-constructed nanoprobe was effective and sensitive for tumor targeting with desirable biosafety. Given its desirable properties such as a 100 nm diameter (capable of penetration of the blood–brain barrier) and bimodal imaging capability, this novel and versatile multimodal nanoprobe could bring a new perspective for elucidating intracranial glioblastoma preoperative diagnosis and the accuracy of tumor resection.

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The Impediments of Cancer Stem Cells and An Exploration into the Nanomedical Solutions for Glioblastoma

Jain

Dhawan

Rao

et al. 2023

ACAMC

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Glioblastoma is an aggressive and reccurent tumour that affects our brain and spinal cord with an extensively poor prognosis and death of the patient within 14-15 months of diagnosis. The tumour originates from astrocytes and therefore comes under the glioma known as astrocytoma. These tumours exhibit miscellaneous properties and contain cancer stem cells (CSCs). The stem cells exhibit diverse mechanisms through which these cells indulge in the proliferation and renewal of their systems. CSCs pose a significant obstacle as far as cancer therapy is concerned, which incorporates blocking important signalling pathways involved in CSCs’ self-renewal and survival which may also include inhibition of the ATP-binding cassette transporters. Nanomedicine, biomarkers and drug delivery technology-based approaches using nanoparticles have tremendous ability to tackle the restrictions impending clinical applications, such as diagnosis and targeting of CSC-specific agents. Nanocarrier-based therapeutic agents have shown a potential of penetrating CSCs and increasing drug accumulation in CSCs. Nanomedicine can overcome ATP-driven pump-mediated multidrug resistance while also reducing the harmful effects on non-cancerous cells. The objective of this review is to examine advantages of nanomedicine and the innovative approaches that have been explored to address the challenges presented by CSCs in order to control the progression of glioblastomas by developing novel nanotherapeutic interventions which target CSCs.

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Identification of Amino Acid Residues in PEPHC1 Important for Binding to the Tumor‐Specific Receptor EGFRvIII

Cited by 3 publications

References 26 publications

Identification of novel peptide ligands for the cancer‐specific receptor mutation EFGRvIII using a mixture‐based synthetic combinatorial library

Identification of novel peptide ligands for the cancer‐specific receptor mutation EFGRvIII using a mixture‐based synthetic combinatorial library

Engineered superparamagnetic iron oxide nanoparticles (SPIONs) for dual-modality imaging of intracranial glioblastoma via EGFRvIII targeting

The Impediments of Cancer Stem Cells and An Exploration into the Nanomedical Solutions for Glioblastoma

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