Landscaping macrocyclic peptides: stapling hDM2-binding peptides for helicity, protein affinity, proteolytic stability and cell uptake
Aline D. de Araujo, Junxian Lim, Kai‐Chen Wu, Huy N. Hoang, Huy The Nguyen, David P. Fairlie
Abstract
+ 7 bridges) in order to sculpt the macrocyclic size, stabilize its structure, and promote cell uptake. We find that rigidifying the macrocycle leads to higher alpha helicity, target affinity and proteolytic stability to different extents, whereas cell uptake of compounds shown here is mostly driven by hydrophobicity and aromaticity of the macrocycle.
Topics & Concepts
PeptideProteasesStereochemistryChemistryLinkerHelix (gastropod)ProteolysisHelicityCleavage (geology)BiochemistryBiophysicsCombinatorial chemistryBiologyEnzymeFracture (geology)Operating systemParticle physicsPaleontologyEcologyPhysicsComputer scienceSnailChemical Synthesis and AnalysisClick Chemistry and ApplicationsUbiquitin and proteasome pathways