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Crosslinked Aspartic Acids as Helix‐Nucleating Templates
Author(s) -
Zhao Hui,
Liu QiSong,
Geng Hao,
Tian Yuan,
Cheng Min,
Jiang YanHong,
Xie MingSheng,
Niu XiaoGang,
Jiang Fan,
Zhang YaOu,
Lao YuanZhi,
Wu YunDong,
Xu NaiHan,
Li ZiGang
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201606833
Subject(s) - aspartic acid , helix (gastropod) , chemistry , peptidomimetic , amine gas treating , template , circular dichroism , substituent , folding (dsp implementation) , stereochemistry , combinatorial chemistry , amino acid , organic chemistry , materials science , biochemistry , nanotechnology , peptide , ecology , engineering , snail , electrical engineering , biology
Described is a facile helix‐nucleating template based on a tethered aspartic acid at the N‐terminus [terminal aspartic acid (TD)]. The nucleating effect of the template is subtly influenced by the substituent at the end of the side‐chain‐end tether as indicated by circular dichroism, nuclear magnetic resonance, and molecular dynamics simulations. Unlike most nucleating strategies, the N‐terminal amine is preserved, thus enabling further modification. Peptidomimetic estrogen receptor modulators (PERMs) constructed using this strategy show improved therapeutic properties. The current strategy can be regarded as a good complement to existing helix‐stabilizing methods.