A VEGFR2 Antagonist and Other Peptoids Evade Immune Recognition

  • John M. Astle
  • D. Gomika Udugamasooriya
  • Joan E. Smallshaw
  • Thomas Kodadek
Article

DOI: 10.1007/s10989-008-9136-1

Cite this article as:
Astle, J.M., Udugamasooriya, D.G., Smallshaw, J.E. et al. Int J Pept Res Ther (2008) 14: 223. doi:10.1007/s10989-008-9136-1

Abstract

We have recently reported a peptoid (N-alkyl-oligoglycine) molecule that binds to the Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) with high affinity and specificity. Moreover, this peptoid is capable of inhibiting VEGFR2 function in vivo (Udugamasooriya et al. J Am Chem Soc 130:5744–5745, 2008) and thus is a lead compound for anti-angiogenic agents. Moreover, the assay developed to identify this VEGFR2 inhibitor is likely to be a general route to peptoid antagonists or agonists of integral membrane receptors. Therefore, it is important to determine whether the VEGFR2-targeted peptoid, and indeed peptoids in general, are inherently immunogenic since an anti-peptoid immune response would significantly complicate their development as therapeutic candidates. In this study, the VEGFR2-targeted peptoid as well as other peptoids of varying lengths were injected into mice along with an immunostimulatory agent. We demonstrate that no significant anti-peptoid immune response is induced. It is further shown that this is not a trivial result of the lack of immunogenicity of a particular peptoid sequence, since conjugation of the peptoids to carrier proteins such as KLH prior to injection induces a robust anti-peptoid immune response. We conclude that free peptoid molecules are not immunogenic, probably due to a lack of T cell epitopes and that peptoid-based therapeutics are therefore not likely to be hindered by anti-peptoid antibody production in most cases.

Keywords

PeptoidsAngiogenesisVEGF receptorImmune responseAntigen

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • John M. Astle
    • 1
    • 2
  • D. Gomika Udugamasooriya
    • 1
    • 2
  • Joan E. Smallshaw
    • 1
    • 2
  • Thomas Kodadek
    • 1
    • 2
  1. 1.Division of Translational Research, Department of Internal Medicine, Center for ImmunologyUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Division of Translational Research, Department of Molecular Biology, Center for ImmunologyUniversity of Texas Southwestern Medical CenterDallasUSA