@article{7e181c31fe21499788bf6d0908dea2e6,
title = "Expanded DNA and RNA Trinucleotide Repeats in Myotonic Dystrophy Type 1 Select Their Own Multitarget, Sequence-Selective Inhibitors",
abstract = "There are few methods available for the rapid discovery of multitarget drugs. Herein, we describe the template-assisted, target-guided discovery of small molecules that recognize d(CTG) in the expanded d(CTG·CAG) sequence and its r(CUG) transcript that cause myotonic dystrophy type 1. A positive cross-selection was performed using a small library of 30 monomeric alkyne- and azide-containing ligands capable of producing >5000 possible di- and trimeric click products. The monomers were incubated with d(CTG)16 or r(CUG)16 under physiological conditions, and both sequences showed selectivity in the proximity-accelerated azide-alkyne [3+2] cycloaddition click reaction. The limited number of click products formed in both selections and the even smaller number of common products suggests that this method is a useful tool for the discovery of single-target and multitarget lead therapeutic agents.",
author = "Hagler, {Lauren D.} and Luu, {Long M.} and Marco Tonelli and Juyeon Lee and Hayes, {Samuel M.} and Bonson, {Sarah E.} and Vergara, {J. Ignacio} and Butcher, {Samuel E.} and Zimmerman, {Steven C.}",
note = "Funding Information: Financial support was provided by the National Institutes of Health (NIH) (R01AR069645 to S.C.Z.) and the National Science Foundation through the Graduate Research Fellow Program under Grant DGE-1746047 (S. E. Bonson). L.D.H. is a member of the NIH Chemistry-Biology Interface Training Grant (NRSA 1-T-32-GM070421). M.T. was supported by NIH Grant P41GM103399. This study made use of the National Magnetic Resonance Facility at Madison, which is supported by NIH Grant P41GM103399. Funding Information: Financial support was provided by the National Institutes of Health (NIH) (R01AR069645 to S.C.Z.) and the National Science Foundation through the Graduate Research Fellow Program under Grant DGE-1746047 (S. E. Bonson). L.D.H. is a member of the NIH Chemistry-Biology Interface Training Grant (NRSA 1-T-32-GM070421). M.T. was supported by NIH Grant P41GM103399. This study made use of the National Magnetic Resonance Facility at Madison, which is supported by NIH Grant P41GM103399. Publisher Copyright: Copyright {\textcopyright} 2020 American Chemical Society.",
year = "2020",
month = sep,
day = "22",
doi = "10.1021/acs.biochem.0c00472",
language = "English",
volume = "59",
pages = "3463--3472",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "37",
}