7wbn | pdb_00007wbn
PDB structure of RevCC
Structural highlights
Publication Abstract from PubMedAlthough interest in stabilized alpha-helical peptides as next-generation therapeutics for modulating biomolecular interfaces is increasing, peptides have limited functionality and stability due to their small size. In comparison, alpha-helical ligands based on proteins can make steric clash with targets due to their large size. Here, we report the design of a monomeric pseudo-isolated alpha-helix (mPIH) system in which proteins behave as if they are peptides. The designed proteins contain alpha-helix ligands that do not require any covalent chemical modification, do not have frayed ends, and importantly can make sterically favorable interactions similar to isolated peptides. An optimal mPIH showed a more than 100-fold increase in target selectivity, which might be related to the advantages in conformational selection due to the absence of frayed ends. The alpha-helical ligand in the mPIH displayed high thermal stability well above human body temperature and showed reversible and rapid folding/unfolding transitions. Thus, mPIH can become a promising protein-based platform for developing stabilized alpha-helix pharmaceuticals. Pseudo-Isolated alpha-Helix Platform for the Recognition of Deep and Narrow Targets.,Kim DI, Han SH, Park H, Choi S, Kaur M, Hwang E, Han SJ, Ryu JY, Cheong HK, Barnwal RP, Lim YB J Am Chem Soc. 2022 Aug 31;144(34):15519-15528. doi: 10.1021/jacs.2c03858. Epub, 2022 Aug 16. PMID:35972994[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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