Crosslinked Aspartic Acids as Helix-Nucleating Templates

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 magneti...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie International Edition 2016-09, Vol.55 (39), p.12088-12093
Main Authors: Zhao, Hui, Liu, Qi-Song, Geng, Hao, Tian, Yuan, Cheng, Min, Jiang, Yan-Hong, Xie, Ming-Sheng, Niu, Xiao-Gang, Jiang, Fan, Zhang, Ya-Ou, Lao, Yuan-Zhi, Wu, Yun-Dong, Xu, Nai-Han, Li, Zi-Gang
Format: Article
Language:English
Subjects:
Acids
amino acids
Aspartic acid
Circular dichroism
Dichroism
Estrogen receptors
Estrogens
helical structures
Modulators
Molecular dynamics
NMR
Nuclear magnetic resonance
peptides
protein-protein interactions
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. The nucleating effect of the template is subtly influenced by substitution tuning on the side‐chain‐end tether. Unlike most nucleating strategies, the N‐terminal NH2 is preserved, thus enabling further modification. Peptidomimetic estrogen receptor modulators constructed with this method show improved therapeutic properties. Dap=2,3‐diaminopropionic acid.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201606833