Identification of heptapeptides interacting with IFN-α-sensitive CML cells.

Abstract

BACKGROUND:

Interferon-alpha (IFN-α) is the traditional therapeutic agent for chronic myeloid leukemia (CML). The molecular mechanism of IFN-α efficacy in the treatment of CML is not fully clear.

OBJECTIVES:

To identify the peptides and/or proteins that bind to the proteins specifically expressed on the surface of IFN-α-sensitive CML cells by using a phage display library.

DESIGN/METHODS:

IFN-α-sensitive KT-1/A3 cells were used as the target, and IFN-α-resistant subline KT-1/A3R was used as absorber for phage display biopanning. The positive phage clones were identified by enzyme-linked immunosorbent assay and flow cytometry. The peptides were deduced from their DNA sequences.

RESULTS:

Multiple clones showed high binding efficiency to KT-1/A3 cells compared with that of the other leukemia cells. One of the peptides, KLWVIPQ, has a partial amino acid sequence homology with the C-terminal domain of E3 ubiquitin-protein ligase.

CONCLUSIONS:

This study presents the identification of specific heptapeptides that bind to IFN-α-sensitive KT-1/A3 cells. The cancer-selective ligands provide novel strategies for early and differential diagnoses, as well as potential targeted drug delivery.

• Authors: Jia Liu, Han-chun Chen, Zhou-zhou Rao, Md Asaduzzaman Khan, Xin-xing Wan, Ai-hua Xu, Nuo Zhang, Dian-zheng Zhang
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 20 Issue 12 Pg. 1583-9 (Dec 2011) ISSN: 1744-7658 [Electronic] England
• PMID: 22092230 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Interferon-alpha
• Peptide Library
• Peptides
• Recombinant Proteins
• Polyethylene Glycols
• Ubiquitin-Protein Ligases
• peginterferon alfa-2a

Topics

• Angiogenesis Inhibitors (metabolism, therapeutic use)
• Base Sequence
• Cell Line, Tumor
• Enzyme-Linked Immunosorbent Assay
• Escherichia coli (drug effects, metabolism)
• Humans
• Interferon-alpha (metabolism, pharmacology, therapeutic use)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, metabolism)
• Molecular Targeted Therapy
• Peptide Library
• Peptides (chemistry, metabolism)
• Polyethylene Glycols (metabolism, therapeutic use)
• Protein Binding
• Recombinant Proteins (metabolism, therapeutic use)
• Sequence Analysis, DNA
• Survival Rate
• Treatment Outcome
• Tumor Cells, Cultured
• Ubiquitin-Protein Ligases (chemistry, metabolism)