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8WGI

Multicyclic peptide molecules targeting ROR1 with high affinity

Summary for 8WGI
Entry DOI10.2210/pdb8wgi/pdb
DescriptorR1-2 (1 entity in total)
Functional Keywordsmulticyclic peptide, disulfide, biosynthetic protein
Biological sourcePhage #D
Total number of polymer chains1
Total formula weight2676.12
Authors
Liu, H.T. (deposition date: 2023-09-21, release date: 2024-09-25, Last modification date: 2025-04-23)
Primary citationLi, J.,Liu, H.,Xiao, S.,Fan, S.,Cheng, X.,Wu, C.
De Novo Discovery of Cysteine Frameworks for Developing Multicyclic Peptide Libraries for Ligand Discovery.
J.Am.Chem.Soc., 145:28264-28275, 2023
Cited by
PubMed Abstract: Conserved cysteine frameworks are essential components of disulfide-rich peptides (DRPs), which dominantly define the structural diversity of both naturally occurring and de novo-designed DRPs. However, there are only very limited numbers of conserved cysteine frameworks, and general methods enabling de novo discovery of cysteine frameworks with robust foldability are still not available. Here, we devised a "touchstone"-based strategy that relies on chasing oxidative foldability between two individual disulfide-rich folds on the phage surface to discover new cysteine frameworks from random sequences. Unique cysteine frameworks with a high degree of compatibility with phage display systems and broad sequence tolerance were successfully identified, which were subsequently exploited for the development of multicyclic DRP libraries, enabling the rapid discovery of new peptide ligands with low-nanomolar and picomolar binding affinity. This study provides an unprecedented method for exploring and exploiting the sequence and structure space of DRPs that is not readily accessible by existing strategies, holding the potential to revolutionize the study of DRPs and significantly advance the design and discovery of multicyclic peptide ligands and drugs.
PubMed: 38092662
DOI: 10.1021/jacs.3c11856
PDB entries with the same primary citation
Experimental method
SOLUTION NMR
Structure validation

238895

数据于2025-07-16公开中

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