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Molecular descriptors suggest stapling as a strategy for optimizing membrane permeability of cyclic peptides
Cyclic peptides represent a promising class of drug candidates. A significant obstacle limiting their development as therapeutics is the lack of an ability to predict their membrane permeability.
ReadMolecular descriptors suggest stapling as a strategy for optimizing membrane permeability of cyclic peptides
Cyclic peptides represent a promising class of drug candidates. A significant obstacle limiting their development as therapeutics is the lack of an ability to predict their membrane permeability.
ReadDStabilize: A Web Resource to Generate Mirror Images of Biomolecules
Peptides comprising D-amino acids have been shown to be resistant to proteolysis. This makes them potential candidates as probes of cellular interactions, notably protein-biomolecule interactions.
ReadIncorporation of Putative Helix-Breaking Amino Acids in the Design of Novel Stapled Peptides: Exploring Biophysical and Cellular Permeability Properties
Stapled α-helical peptides represent an emerging superclass of macrocyclic molecules with drug-like properties, including high-affinity target binding, protease resistance, and membrane permeability. As a model system for probing the chemical space available for optimizing these properties, we focused on dual Mdm2/MdmX antagonist stapled peptides related to the p53 N-terminus.
ReadInhibiting S100B(ββ) for Activating Wild-Type p53: Design of Stapled Peptides
S100B(ββ) is a member of the S100B protein family and is distributed in a cell-specific manner. Its levels are elevated in several cancers such as malignant melanoma and correlate directly with poor prognosis in patients. S100B(ββ) directly interacts with the tumor suppressor p53, inhibiting tetramerization and protein kinase C-dependent phosphorylation, consequently decreasing p53 DNA binding and transcriptional activity, and preventing apoptosis.
ReadComparison of Charge Derivation Methods Applied to Amino Acid Parametrization
When using non-natural amino acids in computational simulations of proteins, it is necessary to ensure appropriate parameterization of the new amino acids toward the creation of appropriate input files. In particular, the charges on the atoms may have to be derived de novo and ad hoc for the new species.
ReadMacrocyclic α helical peptide therapeutic modality: A perspective of learnings and challenges
Macrocyclic α-helical peptides have emerged as a compelling new therapeutic modality to tackle targets confined to the intracellular compartment. Within the scope of hydrocarbon-stapling there has been significant progress to date, including the first stapled α-helical peptide to enter into clinical trials.
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