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Development of homomultimers and heteromultimers of lung cancer-specific peptoids

Authors

  • Jared C. Hooks,

    1. Advanced Imaging Research Center, UT-Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas 75390, TX
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  • Jaya P. Matharage,

    1. Advanced Imaging Research Center, UT-Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas 75390, TX
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  • D. Gomika Udugamasooriya

    Corresponding author
    1. Advanced Imaging Research Center, UT-Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas 75390, TX
    2. Department of Biochemistry, UT-Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas 75390, TX
    • Advanced Imaging Research Center, UT-Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas 75390, TX
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  • This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

Abstract

Multimeric interactions that occur in biology provide impetus for chemists to explore new types of synthetic multivalent ligands that alter cellular functions by mechanisms inaccessible to natural substances. While many different molecules such as peptides, antibody fragments, carbohydrates and organic moieties have been used in developing multimeric ligands, it is worth exploring other important molecular types that have hardly been tested in developing multimeric compounds. Peptoids are one such class of compounds with highly facile synthesis as well as much better biologically amenable qualities. Recently, we identified two HCC4017 lung cancer cell targeting peptoids. Here we explore the possibility of synthesizing multimers of these compounds completely through a solid phase synthesis approach. We have synthesized mini-libraries of homodimers, homotrimers and most importantly, heterodimers of our lung cancer specific compounds. The idea is to develop series of compounds that only differs by the linker portion, which is readily adjustable within the library. The purpose of this is to find the optimal distance between each monomeric unit of the multimer that allows them to perfectly interact with their individual biological targets displayed on the cell surface. Future screens of these minilibraries will identify the multimers with improved binding affinities. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 567–577, 2011.

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