6HFA

Crystal structure of hDM2 in complex with a C-terminal triurea capped peptide chimera foldamer.

6HFA の概要

• エントリーDOI: 10.2210/pdb6hfa/pdb
• 分子名称: E3 ubiquitin-protein ligase Mdm2, LM266, 1-[(2~{S})-2-azanyl-3-methyl-butyl]urea (3 entities in total)
• 機能のキーワード: protein foldamer complex, protein protein interaction inhibitor, urea based chimera foldamer, oncoprotein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 25253.41

構造登録者

Buratto, J.,Mauran, L.,Goudreau, S.,Fribourg, S.,Guichard, G. (登録日: 2018-08-21, 公開日: 2020-07-08, 最終更新日: 2024-11-13)

主引用文献

Cussol, L.,Mauran-Ambrosino, L.,Buratto, J.,Belorusova, A.Y.,Neuville, M.,Osz, J.,Fribourg, S.,Fremaux, J.,Dolain, C.,Goudreau, S.R.,Rochel, N.,Guichard, G.
Structural Basis for alpha-Helix Mimicry and Inhibition of Protein-Protein Interactions with Oligourea Foldamers.
Angew.Chem.Int.Ed.Engl., 2020

PubMed Abstract: Efficient optimization of a peptide lead into a drug candidate frequently needs further transformation to augment properties such as bioavailability. Among the different options, foldamers, which are sequence-based oligomers with precise folded conformation, have emerged as a promising technology. We introduce oligourea foldamers to reduce the peptide character of inhibitors of protein-protein interactions (PPI). However, the precise design of such mimics is currently limited by the lack of structural information on how these foldamers adapt to protein surfaces. We report a collection of X-ray structures of peptide-oligourea hybrids in complex with ubiquitin ligase MDM2 and vitamin D receptor and show how such hybrid oligomers can be designed to bind with high affinity to protein targets. This work should enable the generation of more effective foldamer-based disruptors of PPIs in the context of peptide lead optimization.

PubMed: 32935897
DOI: 10.1002/anie.202008992

実験手法

X-RAY DIFFRACTION (1.79 Å)