@article{92c4bcec901449f29b9e5bce31cb2d16,
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 = "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. 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.",
year = "2020",
month = sep,
day = "22",
doi = "10.1021/acs.biochem.0c00472",
language = "English (US)",
volume = "59",
pages = "3463--3472",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "37",
}