Unconventional Secondary Structure Mimics: Ladder-Rungs |
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Authors: | Dr Chen-Ming Lin Maritess Arancillo Jonathan Whisenant Prof Kevin Burgess |
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Institution: | 1. Department of Chemistry, Texas A&M University, Box 30012, College Station, TX, 77842 USA
These authors contributed equally to this work.;2. Department of Chemistry, Texas A&M University, Box 30012, College Station, TX, 77842 USA |
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Abstract: | Secondary structures tend to be recognizable because they have repeating structural motifs, but mimicry of these does not have to follow such well-defined patterns. Bioinformatics studies to match side-chain orientations of a novel hydantoin triazole chemotype ( 1 ) to protein-protein interfaces revealed it tends to align well across parallel and antiparallel sheets, like rungs on a ladder. One set of these overlays was observed for the protein-protein interaction uPA?uPAR. Consequently, chemotype 1 was made with appropriate side-chains to mimic uPA at this interface. Biophysical assays indicate these compounds did in fact bind uPAR, and elicit cellular responses that affected invasion, migration, and wound healing. |
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Keywords: | cancer peptide peptidomimetics protein–protein interactions uPAR |
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