Unconventional Secondary Structure Mimics: Ladder‐Rungs
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 20, 2020
- Source ID
- 10.1002/ange.202002639
Entities
People
- Chen‐ming Lin
- Jonathan Whisenant
- Kevin Burgess
- Maritess Arancillo
Organizations
- Cancer Prevention and Research Institute of Texas
- National Institutes of Health
- National Science Foundation
- Robert A. Welch Foundation
- United States Army
- Yusuf Hamied Department of Chemistry