title: Design of a PKCδ-specific small peptide as a theragnostic agent for glioblastoma.
abstract: Glioblastoma is an aggressive malignant brain tumor that starts in the brain or spine and frequently recurs after anticancer treatment. The development of an accurate diagnostic system combined with effective cancer therapy is essential to improve prognosis of glioma patients. Peptides, produced from phage display, are attractive biomolecules for glioma treatment because of their biostability, nontoxicity, and small size. In this study, we employed phage display methodology to screen for peptides that specifically recognize the target PKCδ as a novel biomarker for glioma. The phage library screening yielded four different peptides displayed on phages with a 20- to 200-pM Kd value for the recombinant PKCδ catalytic domain. Among these four phage peptides, we selected one to synthesize and tagged it with fluorescein isothiocyanate (FITC) based on the sequence of the PKCδ-binding phage clone. The synthetic peptide showed a relative binding affinity for antibody and localization in the U373 glioma cell. The kinase activity of PKCδ was inhibited by FITC-labeled peptide with an IC50 of 1.4 μM in vitro. Consequently, the peptide found in this study might be a promising therapeutic agent against malignant brain tumor.
authors.affiliation: Department of Chemistry and Institute for Natural Sciences, Hanyang University, Seoul 133-791, South Korea.
authors.forename: Jun-Haeng
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Chemistry and Institute for Natural Sciences, Hanyang University, Seoul 133-791, South Korea.
authors.forename: Na-Reum
authors.initials: NR
authors.lastname: Ha
authors.affiliation: Department of Neurology, Hanyang University, Seoul 133-791, South Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Koh
authors.affiliation: Department of Chemistry and Institute for Natural Sciences, Hanyang University, Seoul 133-791, South Korea. Electronic address: myyoon@hanyang.ac.kr.
authors.forename: Moon-Young
authors.initials: MY
authors.lastname: Yoon
mesh_terms: D001932:Brain Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D005909:Glioblastoma / Q000175:diagnosis* / Q000628:therapy*; D006801:Humans; D051745:Protein Kinase C-delta / Q000737:chemistry*; D000068936:Theranostic Nanomedicine
chemical_list: D051745:Protein Kinase C-delta
keywords: Brain glioma; Cancer stem cell; PKC; Peptide; Phage display