Tan YS
Kinetic and thermodynamic effects of phosphorylation on p53 binding to MDM2
p53 is frequently mutated in human cancers. Its levels are tightly regulated by the E3 ubiquitin ligase MDM2. The complex between MDM2 and p53 is largely formed by the interaction between the N-terminal domain of MDM2 and the N-terminal transactivation (TA) domain of p53 (residues 15-29).
ReadTargeting cancer addiction for SALL4 by shifting its transcriptome with a pharmacologic peptide
Sal-like 4 (SALL4) is a nuclear factor central to the maintenance of stem cell pluripotency and is a key component in hepatocellular carcinoma, a malignancy with no effective treatment. In cancer cells, SALL4 associates with nucleosome remodeling deacetylase (NuRD) to silence tumor-suppressor genes, such as PTEN.
ReadStapled peptides as a new technology to investigate protein-protein interactions in human platelets.
Platelets are blood cells with numerous crucial pathophysiological roles in hemostasis, cardiovascular thrombotic events and cancer metastasis. Platelet activation requires the engagement of intracellular signalling pathways that involve protein–protein interactions (PPIs).
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.
ReadRole of the N-terminal lid in regulating the interaction of phosphorylated MDMX with p53
Murine double minute 4 protein (MDMX) is crucial for the regulation of the tumor suppressor protein p53. Phosphorylation of the N-terminal domain of MDMX is thought to affect its binding with the transactivation domain of p53, thus playing a role in p53 regulation. In this study, the effects of MDMX phosphorylation on the binding of p53 were investigated using molecular dynamics simulations.
ReadAn Intramolecular Tryptophan-Condensation Approach for Peptide Stapling
Stapled peptides are gaining tremendous interest as next-generation therapeutic agents to target protein–protein interactions.
Read