6IMH

Solution Structure of Bicyclic Peptide pb-18

Summary for 6IMH

• Entry DOI: 10.2210/pdb6imh/pdb
• Descriptor: (ACE)-GLY-CYS-PRO-CYS-GLU-PRO-SER-TYR-LEU-CYS-PRO-TRP-LEU-PRO-GLY-CYS-(NH2) (1 entity in total)
• Functional Keywords: bicyclic peptide, cystine bridge, proline rich, de novo protein
• Biological source: Enterobacteria phage M13
• Total number of polymer chains: 1
• Total formula weight: 1749.09

Authors

Yao, H.,Lin, P.,Zha, J.,Zha, M.,Zhao, Y.,Wu, C. (deposition date: 2018-10-22, release date: 2019-08-28, Last modification date: 2024-11-06)

Primary citation

Lin, P.,Yao, H.,Zha, J.,Zhao, Y.,Wu, C.
Ordered and Isomerically Stable Bicyclic Peptide Scaffolds Constrained through Cystine Bridges and Proline Turns.
Chembiochem, 20:1514-1518, 2019

PubMed Abstract: Bicyclic peptides are attractive scaffolds for the design of potent protein binders and new therapeutics. However, peptide bicycles constrained through disulfide bonds are rarely stable or tolerant to sequence manipulation owing to disulfide isomerization, especially for peptides lacking a regular secondary structure. Herein, we report the discovery and identification of a class of bicyclic peptide scaffolds with ordered but irregular secondary structures. These peptides have a conserved cysteine/proline framework for directing the oxidative folding into a fused bicyclic structure that consists of four irregular turns and a 3 helix (characterized by NMR spectroscopy). This work shows that bicyclic peptides can be stabilized into ordered structures by manipulating both the disulfide bonds and proline-stabilized turns. In turn, this could inspire the design and engineering of multicyclic peptides with new structures and benefit the development of novel protein binders and therapeutics.

PubMed: 30770638
DOI: 10.1002/cbic.201800788

Experimental method

SOLUTION NMR