RRC ID 53861
Author Toyama K, Nomura W, Kobayakawa T, Tamamura H.
Title Delivery of a Proapoptotic Peptide to EGFR-Positive Cancer Cells by a Cyclic Peptide Mimicking the Dimerization Arm Structure of EGFR.
Journal Bioconjug. Chem.
Abstract A cyclic decapeptide, CQTPYYMNTC (1), which mimics the dimerization arm of the EGF receptor (EGFR), was previously found to be captured into cells. We have sought to investigate the promising potential of this peptide as an intracellular delivery vehicle directed to EGFR-positive cells. The selectivity of peptide 1 to the EGFR was confirmed by a positive correlation between the expression level of the receptor and the cellular uptake of peptide 1 as shown by siRNA knockdown of the EGFR. The proapoptotic domain (PAD) peptide ([KLAKLAK]2) has limited use due to a deficiency of cell membrane permeability resulting from cationic sequences and lack of specificity for cancer cells. As a proof-of-concept study, the cellular delivery of the PAD peptide was challenged by conjugation with peptide 1. The cellular uptake of a conjugated peptide 2, which was composed of peptide 1, the PAD peptide, and a linker cleavable with a protease, was evaluated by treatment of an EGFR-positive lung carcinoma cell line, A549. Significant suppression of proliferation by peptide 2 was shown in the results of a cell viability assay. The PAD peptide alone had no effect on the cells. The results suggest that peptide 1 is a promising lead compound as a new intracellular delivery vehicle for therapeutically effective peptides.
Volume 29(6)
Pages 2050-2057
Published 2018-6-20
DOI 10.1021/acs.bioconjchem.8b00250
PMID 29763296
MeSH A549 Cells Adenocarcinoma of Lung / drug therapy Adenocarcinoma of Lung / metabolism Amino Acid Sequence Antineoplastic Agents / administration & dosage* Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacokinetics Antineoplastic Agents / pharmacology* Apoptosis / drug effects* Cell Proliferation / drug effects Drug Delivery Systems ErbB Receptors / chemistry ErbB Receptors / metabolism Humans Lung Neoplasms / drug therapy Lung Neoplasms / metabolism Models, Molecular Peptides / administration & dosage* Peptides / chemistry Peptides / pharmacokinetics Peptides / pharmacology* Peptides, Cyclic / administration & dosage Peptides, Cyclic / chemistry Peptides, Cyclic / pharmacokinetics Peptides, Cyclic / pharmacology Protein Multimerization
IF 4.485
Human and Animal Cells A431(RCB0202), A549(RCB0098), 293(RCB1637)