9CY8

Constrained b-hairpins targeting the EphA4 ligand binding domain

これはPDB形式変換不可エントリーです。

9CY8 の概要

• エントリーDOI: 10.2210/pdb9cy8/pdb
• 分子名称: Ephrin type-A receptor 4, Constrained b-hairpin, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: receptor tyrosine kinase epha4, lipid binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22813.29

構造登録者

Muzzarelli, K.M.,Assar, Z.,Prentis, A.M.,Baggio, C.,Pellecchia, M. (登録日: 2024-08-01, 公開日: 2024-12-25, 最終更新日: 2025-01-01)

主引用文献

Prentiss, A.M.,Baggio, C.,Pagett, J.,Kulinich, A.O.,Ethell, I.M.,Muzzarelli, K.,Assar, Z.,Pellecchia, M.
Constrained beta-Hairpins Targeting the EphA4 Ligand Binding Domain.
J.Med.Chem., 67:22245-22253, 2024

PubMed Abstract: The activity of the receptor tyrosine kinase EphA4 has been implicated in several pathologies including oncology (gastric and pancreatic cancers) and neurodegenerative diseases (amyotrophic lateral sclerosis and Alzheimer's disease). However, advances in validating EphA4 as a possible drug target have been limited by the lack of suitable pharmacological inhibitors. Recently, we reported on the design of potent EphA4 agonistic agents targeting its ligand binding domain (LBD). Based on previous studies with a phage display cyclic peptide inhibitor, we designed a β-hairpin mimetic with high affinity for EphA4-LBD. These agents hold great promise for further validation and development of EphA4-based therapeutics. Moreover, our studies introduce a possible strategy for the design of constrained β-hairpin peptides.

PubMed: 39656022
DOI: 10.1021/acs.jmedchem.4c02286

実験手法

X-RAY DIFFRACTION (2.5 Å)