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Effect of Stapling Architecture on Physiochemical Properties and Cell Permeability of Stapled α‐Helical Peptides: A Comparative Study
Author(s) -
Tian Yuan,
Jiang Yanhong,
Li Jingxu,
Wang Dongyuan,
Zhao Hui,
Li Zigang
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700352
Subject(s) - cell permeability , intracellular , biophysics , cell , peptide , chemistry , cell penetrating peptide , amphiphile , membrane , permeability (electromagnetism) , penetration (warfare) , biochemistry , combinatorial chemistry , biology , organic chemistry , copolymer , polymer , operations research , engineering
Stapled peptides have emerged as a new class of targeting molecules with high binding affinity and specificity for intracellular undruggable targets. Their ability to penetrate cell membranes is exceptionally intriguing but remains elusively and controversially discussed. To understand the effect of stapling architectures on their physiochemical properties and to aid in promoting their cell permeability, we report herein a comparative study on the physiochemical properties and cell permeability of stapled α‐helical peptides with different types of crosslinks. We highlight the decisive impact of the intrinsic properties of the crosslinks on cell permeability rather than the helical contents of the peptides in model amphipathic sequences targeting estrogen receptor–coactivator interaction. We envision this finding to shed further light on the chemical optimization of stapled α‐helical peptides or macrocyclic cell‐penetrating peptides for enhanced cell penetration.