Abstract
Our NMR, IR/Raman, CD spectroscopic, and X-ray crystallographic studies, as well as accelerated molecular dynamics simulations, showed that alternating hybrid α/β-peptides containing a bicyclic β-proline surrogate form unique extended curved folds, regardless of the peptide length and solvent environment. It is suggested that extended β/PPII structures are preferred in the insulating α-alanine moieties between the rigid bicyclic β-proline structures. These hybrid peptides inhibit p53-MDM2 and p53-MDMX protein-protein interactions.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Cell Cycle Proteins / antagonists & inhibitors
-
Cell Cycle Proteins / chemistry
-
Crystallography, X-Ray
-
Humans
-
Molecular Dynamics Simulation
-
Peptides / chemistry*
-
Peptides / pharmacology
-
Proline / analogs & derivatives*
-
Proline / chemistry
-
Proline / pharmacology
-
Protein Binding / drug effects
-
Protein Structure, Secondary
-
Proto-Oncogene Proteins / antagonists & inhibitors
-
Proto-Oncogene Proteins / chemistry
-
Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors
-
Proto-Oncogene Proteins c-mdm2 / chemistry
-
Tumor Suppressor Protein p53 / antagonists & inhibitors
-
Tumor Suppressor Protein p53 / chemistry
Substances
-
Cell Cycle Proteins
-
MDM4 protein, human
-
Peptides
-
Proto-Oncogene Proteins
-
Tumor Suppressor Protein p53
-
Proline
-
Proto-Oncogene Proteins c-mdm2
-
beta-proline