We report here a chemoselective peptide "stapling" method that can be performed on ligand-receptor complexes in situ. An appropriately structured macrocyclic bis-oxime linkage is shown to improve the affinity of a peptide ligand for its native protein receptor. The presence of the receptor as a template to preorganize the ligand into its bioactive conformation is found to bias reaction outcomes...

Objective(s): Fabricating a biomimetic scaffold platform combined with controlled release of bioactive agents is a practical approach for bone tissue engineering. Controlled delivery of peptides and growth factors which play a significant role in osteogenesis is an important issue reducing the associated adverse effects and leading to cost-effectiveness. Materials and Methods: We develope...

It is hypothesized that different ligand-induced conformational changes can explain the different interactions of nuclear receptors with regulatory proteins, resulting in specific biological activities. Understanding the mechanism of how ligands regulate cofactor interaction facilitates drug design. To investigate these ligand-induced conformational changes at the surface of proteins, we perfor...

Abstract Noncovalent bonds typically mediate interactions between a T cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) ligand. In this study, we describe novel mechanism involving covalent TCR-pMHC interaction through cysteine-cysteine disulfide bond. By introducing cysteine resodues into the TCR CDR3 peptide of known combination, show that bond formation does not require...

The use of peptide libraries for the identification and characterization of T cell antigen peptide epitopes and mimotopes has been hampered by the need to form complexes between the peptides and an appropriate MHC molecule in order to construct a complete T cell ligand. We have developed a baculovirus-based peptide library method in which the sequence encoding the peptide is embedded within the...

The de facto commoditization of biomolecular crystallography as a result of almost disruptive instrumentation automation and continuing improvement of software allows any sensibly trained structural biologist to conduct crystallographic studies of biomolecules with reasonably valid outcomes: that is, models based on properly interpreted electron density. Robust validation has led to major mista...

The binding mode of natural peptide ligands to the Y5 G protein-coupled receptor (Y5R), an attractive therapeutic target for treatment obesity, is largely unknown. Here, we apply complementary biochemical and computational approaches, including scanning surface with a genetically encoded crosslinker, Ala-scanning ligand double-cycle mutagenesis, map interactions in ligand-receptor interface bui...

Cardiovascular diseases (CVDs) like hypertension are a major cause for death worldwide. In the cardiovascular tissue, endothelin system—consisting of receptor subtypes A (ETAR) and B (ETBR) mixed agonist 1 (ET-1)—is key player in regulation vascular tone blood pressure. Tight control this system is required to maintain homeostasis; otherwise, can severe CVDs pulmonary artery hypertension. The h...