2M77

[Asp2]RTD-1

2M77 の概要

• エントリーDOI: 10.2210/pdb2m77/pdb
• 関連するPDBエントリー: 2LYF 2M78 2M79
• NMR情報: BMRB: 19175
• 分子名称: [Asp2]RTD-1 (1 entity in total)
• 機能のキーワード: theta-defensin, cyclic peptides, cyclic cystine ladder, integrin-binding, cell adhesion
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2078.58

構造登録者

Conibear, A.C.,Bochen, A.,Rosengren, K.,Kessler, H.,Craik, D.J. (登録日: 2013-04-18, 公開日: 2014-02-05, 最終更新日: 2024-11-20)

主引用文献

Conibear, A.C.,Bochen, A.,Rosengren, K.J.,Stupar, P.,Wang, C.,Kessler, H.,Craik, D.J.
The Cyclic Cystine Ladder of Theta-Defensins as a Stable, Bifunctional Scaffold: A Proof-of-Concept Study Using the Integrin-Binding RGD Motif
Chembiochem, 15:451-459, 2014

PubMed Abstract: Peptides have the specificity and size required to target the protein-protein interactions involved in many diseases. Some cyclic peptides have been utilised as scaffolds for peptide drugs because of their stability; however, other cyclic peptide scaffolds remain to be explored. θ-Defensins are cyclic peptides from mammals; they are characterised by a cyclic cystine ladder motif and have low haemolytic and cytotoxic activity. Here we demonstrate the potential of the cyclic cystine ladder as a scaffold for peptide drug design by introducing the integrin-binding Arg-Gly-Asp (RGD) motif into the θ-defensin RTD-1. The most active analogue had an IC50 of 18 nM for the αv β3 integrin as well as high serum stability, thus demonstrating that a desired bioactivity can be imparted to the cyclic cystine ladder. This study highlights how θ-defensins can provide a stable and conformationally restrained scaffold for bioactive epitopes in a β-strand or turn conformation. Furthermore, the symmetry of the cyclic cystine ladder presents the opportunity to design peptides with dual bioactive epitopes to increase activity and specificity.

PubMed: 24382674
DOI: 10.1002/cbic.201300568

実験手法

SOLUTION NMR