2M78

[Asp11]RTD-1

Summary for 2M78

• Entry DOI: 10.2210/pdb2m78/pdb
• Related: 2LYF 2M77 2M79
• NMR Information: BMRB: 19176
• Descriptor: [Asp11]RTD-1 (1 entity in total)
• Functional Keywords: theta-defensin, cyclic peptides, cyclic cystine ladder, integrin-binding, cell adhesion
• Total number of polymer chains: 1
• Total formula weight: 2126.63

Authors

Conibear, A.C.,Bochen, A.,Rosengren, K.,Kessler, H.,Craik, D.J. (deposition date: 2013-04-19, release date: 2014-02-05, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

SOLUTION NMR