Skip Navigation

JNCI Journal of the National Cancer Institute 2006 98(13):932-936; doi:10.1093/jnci/djj247
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplemental Information
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (6)
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Dings, R. P. M.
Right arrow Articles by Mayo, K. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dings, R. P. M.
Right arrow Articles by Mayo, K. H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press.

BRIEF COMMUNICATION

Design of Nonpeptidic Topomimetics of Antiangiogenic Proteins With Antitumor Activities

Ruud P. M. Dings, Xuemei Chen, Debby M. E. I. Hellebrekers, Loes I. van Eijk, Ying Zhang, Thomas R. Hoye, Arjan W. Griffioen, Kevin H. Mayo

Affiliations of authors: Departments of Biochemistry, Molecular Biology & Biophysics (RPMD, KHM) and Chemistry (XC, TRH) and the Cancer Center (YZ, KHM), University of Minnesota, Minneapolis, MN; Angiogenesis Laboratory, Research Institute for Growth and Development, Department of Pathology, University Hospital Maastricht, The Netherlands (DMEIH, LIvE, AWG)

Correspondence to: Kevin H. Mayo, PhD, Department of Biochemistry, 6-155 Jackson Hall, University of Minnesota, 321 Church Street, Minneapolis, MN 55455 (e-mail: mayox001{at}umn.edu).

The inhibition of angiogenesis is a promising avenue for cancer treatment. Although some angiostatic compounds are in the process of development and testing, these often prove ineffective in vivo or have unwanted side effects. We have designed, synthesized, and evaluated a small library of nonpeptidic, calixarene-based protein surface topomimetics that display chemical substituents to approximate the molecular dimensions and amphipathic features (hydrophobic and positively charged residues) of the antiangiogenic peptide anginex, which, like many antiangiogenic proteins, consists primarily of an antiparallel beta-sheet structure as the functional unit. Two of the topomimetics (0118 and 1097) were potent angiogenesis inhibitors in vitro, as determined by endothelial cell proliferation, migration, and chick embryo chorioallantoic membrane assays. Moreover, both compounds were highly effective at inhibiting tumor angiogenesis and growth in two mouse models (MA148 human ovarian carcinoma and B16 murine melanoma). Our results demonstrate the feasibility of designing nonpeptidic protein surface topomimetics as novel pharmaceutical agents for clinical intervention against cancer through angiostatic or other mechanisms.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
R. P.M. Dings, M. Loren, H. Heun, E. McNiel, A. W. Griffioen, K. H. Mayo, and R. J. Griffin
Scheduling of Radiation with Angiogenesis Inhibitors Anginex and Avastin Improves Therapeutic Outcome via Vessel Normalization
Clin. Cancer Res., June 1, 2007; 13(11): 3395 - 3402.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.