Macrocyclic Peptides Uncover a Novel Binding Mode for Reversible Inhibitors of LSD1
Jie Yang, V. Talibov, Stefan Peintner, Claire Rhee, Vasanthanathan Poongavanam, Matthis Geitmann, Matteo Rossi Sebastiano, Bernd Simon, Janosch Hennig, Doreen Dobritzsch, U. Helena Danielson, Jan Kihlberg
Abstract
suggests that macrocyclization restricts its solution ensemble to conformations that include the one in the crystalline complex. Our results provide a solid basis for the design of optimized reversible LSD1 inhibitors.
Topics & Concepts
DemethylasePeptideChemistryStereochemistryHistone H3Rational designHistoneBinding siteNuclear magnetic resonance spectroscopyTransferaseEnzymeLysineCrystallographyBiochemistryAmino acidBiologyGeneticsDNAEpigenetics and DNA MethylationChemical Synthesis and AnalysisHistone Deacetylase Inhibitors Research