Rationally designed anti-HER2/neu peptide mimetic disables P185HER2/neu tyrosine kinases in vitro and in vivo

Park, Byeong Woo; Zhang, Hong Tao; Wu, Changjiang; Berezov, Alan; Zhang, Xin; Dua, Raj; Wang, Qiang; Kao, Gary; O’Rourke, Donald M.; Greene, Mark I.; Murali, Ramachandran

doi:10.1038/72651

Cited by 177 publications

(152 citation statements)

References 37 publications

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“…A colorectal cancer targeting therapeutical may also be developed by combining the sequence with a cytotoxic compound. 11,16 However, because therapeutic treatment implies in vivo use, it will be important to know the in vivo specificity of the selected peptide sequence by determining the binding efficiencies to different normal human tissues. Because any given receptor may be expressed in several cell types at different levels and times, one has to exclude any unwanted binding to healthy tissue.…”

Section: Discussionmentioning

confidence: 99%

“…15 Unspecific control peptides contained the GHLIPLRQPSHQ sequence ( GHL ), a sequence that was found in a phage with no selectivity to any cells or organ. Thus, the following peptides were used: HEW-K 16 : HEWSYLAPYPWFK 16 , HEW-C1q: HEWSY-LAPYPWFCRAPDGKKGEAGRPGRRGRPGLK, and the controls: GHL -K 16 : GHLIPLRQPSHQK 16 , and GHL -C1q: GHLIPLRQPSHQCRAPDGKKGEAGRPGRRGRPGLK. All peptides were reconstituted in H 2 O.…”

Section: Cancer Gene Therapymentioning

confidence: 99%

“…We tested peptides with the specific HEW sequence and with either of two different cationic peptide sequences (K 16 or C1q ) at the C -terminal end. The cationic peptides have DNA -condensing abilities and might be useful for transfections.…”

Section: Cancer Gene Therapymentioning

confidence: 99%

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Tumor cell-targeting by phage-displayed peptides

et al. 2002

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We isolated cancer cell -specific phages by subtracting and selecting complex peptide display phage libraries on cultured human cancer cells. The best candidate was selected by performing three rounds of subtraction before each of five selections on the human colorectal WiDr cell line. The phage showed more than 1000 -fold higher binding efficiency for WiDr cells when compared to five other human cancer cell lines, including two of colorectal origin, and when compared to wild -type M13 phage. Fifty -fold higher binding efficiency was also seen for a human breast cancer cell line. We show that the WiDr cell binding of the selected phage was efficiently competed by the synthetic peptide HEWSYLAPYPWF, predicted from the phage sequence. This confirms that the specificity of the peptide is independent of the display by the phage coat proteins. The identified peptide may target biomarkers linked to colorectal cancer, and thus be useful for designing gene transfer vectors as well as diagnostic and prognostic tools for this disease.

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Section: Discussionmentioning

confidence: 99%

Section: Cancer Gene Therapymentioning

confidence: 99%

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Tumor cell-targeting by phage-displayed peptides

et al. 2002

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“…Modifying polymer vesicles with biological ligands enables targeting of upregulated receptors and molecules on affected cells in vitro and in vivo, thereby enhancing the nanoparticles' EPR effect and further mitigating the potential toxic side effects of systemic delivery. Additionally, chemotherapeutics, when used in conjunction with molecular targeting agents, can have a synergistic effect [59]. In addition to therapeutic applications, over the past two decades the use of anticancer antibodies against molecular targets has been developed for tumor imaging applications [37].…”

Section: Polymersome Surface Modifications For Delivery and Therapymentioning

confidence: 99%

“…We have recently attempted to conjugate small anti-HER2/ neu peptidomimetics, designed by Murali and coworkers [59], to polymersomes in order to further develop these nanoparticles for both clinical breast cancer diagnosis (NIR-emissive polymer-somes) and therapy (e.g. with and without doxorubicin incorporation).…”

Section: Polymersome Surface Modifications For Delivery and Therapymentioning

confidence: 99%

Polymersomes: A new multi-functional tool for cancer diagnosis and therapy

Levine

Ghoroghchian

Freudenberg

et al. 2008

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Nanoparticles are being developed as delivery vehicles for therapeutic pharmaceuticals and contrast imaging agents. Polymersomes (mesoscopic polymer vesicles) possess a number of attractive biomaterial properties that make them ideal for these applications. Synthetic control over block copolymer chemistry enables tunable design of polymersome material properties. The polymersome architecture, with its large hydrophilic reservoir and its thick hydrophobic lamellar membrane, provides significant storage capacity for both water soluble and insoluble substances (such as drugs and imaging probes). Further, the brush-like architecture of the polymersome outer shell can potentially increase biocompatibility and blood circulation times. A further recent advance is the development of multi-functional polymersomes that carry pharmaceuticals and imaging agents simultaneously. The ability to conjugate biologically active ligands to the brush surface provides a further means for targeted therapy and imaging. Hence, polymersomes hold enormous potential as nanostructured biomaterials for future in vivo drug delivery and diagnostic imaging applications.

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Selection of peptides and synthesis of pentameric peptabody molecules reacting specifically with ErbB-2 receptor

et al. 2001

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The HER‐2/ErbB‐2 oncoprotein is overexpressed in human breast and ovarian adenocarcinomas and is clearly associated with the malignant phenotype. Although no specific ligand for this receptor has been positively identified, ErbB‐2 was shown to play a central role in a network of interactions with the related ErbB‐1, ErbB‐3 and ErbB‐4 receptors. We have selected new peptides binding to ErbB‐2 extracellular domain protein (ECD) by screening 2 newly developed constrained and unconstrained random hexapeptide phage libraries. Out of 37 phage clones, which bound specifically to ErbB‐2 ECD, we found 6 constrained and 10 linear different hexapeptide sequences. Among the latter, 5 consensus motifs, all with a common methionine and a positively charged residue at positions 1 and 3, respectively, were identified. Furthermore, 3 representative hexapeptides were fused to a coiled‐coil pentameric recombinant protein to form the so‐called peptabodies recently developed in our laboratory. The 3 peptabodies bound specifically to the ErbB‐2 ECD, as determined by enzyme‐linked immunosorbent assay and BIAcore analysis and to tumor cells overexpressing ErbB‐2, as shown by flow cytometry. Interestingly, one of the free selected linear peptides and all 3 peptabodies inhibited the proliferation of tumor cells overexpressing ErbB‐2. In conclusion, a novel type of ErbB‐2‐specific ligand is described that might complement presently available monoclonal antibodies. © 2001 Wiley‐Liss, Inc.

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Rationally designed anti-HER2/neu peptide mimetic disables P185HER2/neu tyrosine kinases in vitro and in vivo

Cited by 177 publications

References 37 publications

Tumor cell-targeting by phage-displayed peptides

Tumor cell-targeting by phage-displayed peptides

Polymersomes: A new multi-functional tool for cancer diagnosis and therapy

Selection of peptides and synthesis of pentameric peptabody molecules reacting specifically with ErbB-2 receptor

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