The co-inhibitory immune checkpoint interaction between programmed cell death-protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) serves to regulate T-cell activation, promoting self-tolerance. Over-expression of PD-L1 is a mechanism through which tumour cells can evade detection by the immune system. Several therapeutic antibodies targeting PD-L1 or PD-1 have been approved for the treatment of a variety of cancers, however, the discovery and development of small-molecule inhibitors of PD-L1 remains a challenge. Here we report comprehensive sequence-specific backbone resonance assignments (H, C, and N) obtained for the N-terminal IgV-like domain of PD-L1 (D1) and the full two domain extracellular region (D1D2). These NMR assignments will serve as a useful tool in the discovery of small-molecule therapeutics targeting PD-L1 and in the characterisation of functional interactions with other protein partners, such as CD80.
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http://dx.doi.org/10.1007/s12104-022-10092-5 | DOI Listing |
J Biomol Struct Dyn
February 2025
Laboratory of Integrative Genomics, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, India.
The P53 protein, a cancer-associated transcriptional factor and tumor suppressor, houses a Zn ion in its DNA-binding domain (DBD), essential for sequence-specific DNA binding. However, common mutations at position 273, specifically from Arginine to Histidine and Cysteine, lead to a loss of function as a tumor suppressor, also called DNA contact mutations. The mutant (MT) P53 structure cannot stabilize DNA due to inadequate interaction.
View Article and Find Full Text PDFClin Rheumatol
December 2024
Immunology and Histocompatibility Department, Hedi Chaker University Hospital, Sfax, Tunisia.
Introduction/objectives: Psoriatic arthritis (PsA) is a chronic inflammatory rheumatism belonging to the spondyloarthritis family. It is a multifactorial disease whose genetic determinism is still poorly understood. It is favored by environmental factors in genetically predisposed individuals.
View Article and Find Full Text PDFOrg Biomol Chem
December 2024
Department of Chemistry, New York University, New York, New York 10003, USA.
We report the use of unprotected amino acids as submonomer reagents in the solid-phase synthesis of -substituted glycine peptoid oligomers. Subsequent coupling of an amine, alcohol, or thiol to the free carboxylate of the incorporated amino acid provides access to peptoids bearing amides, esters, and thioesters as side chain pendant groups and permits further elongation of the peptoid backbone. The palette of readily obtained building blocks suitable for solid-phase peptoid synthesis is substantially expanded through this protocol, further enhancing the chemical diversity and potential applications of sequence-specific peptoid oligomers.
View Article and Find Full Text PDFJ Chromatogr A
November 2024
Manitoba Centre for Proteomics and Systems Biology, Health Science Centre, Winnipeg, MB R3E 3P4, Canada; Department of Internal Medicine, University of Manitoba, Winnipeg, MB R3E 3P4, Canada. Electronic address:
Electrostatic Repulsion-Hydrophilic Interaction Chromatography (ERLIC) is one of the legacy separation tools developed by Dr. Andrew Alpert and has been used for developing unique separation methods of hydrophilic compounds, including peptides. In the past it has been studied using designed peptide libraries to elucidate major features of its separation mechanism, while comprehensive peptide retention modeling for ERLIC is still lacking.
View Article and Find Full Text PDFBiophys Chem
December 2024
Graduate School of Science and Engineering, Tokyo Metropolitan University, 1-1 Minami-ohsawa, Hachioji, Tokyo 192-0397, Japan. Electronic address:
The observation of side-chain peaks of aromatic amino acids is the prerequisite for a high-resolution three-dimensional structure determination of proteins by NMR. However, it becomes difficult with increasing molecular size due to an increased transverse relaxation and the control of the relaxation pathway is needed to achieve the observation. We demonstrated that even for the large molecular size of 82 kDa Malate synthase G (MSG), the aromatic C-H (CH) peaks of Tryptophan (Trp) and Phenylalanine (Phe) residues can be observed with high quality using a systematic stable isotope labeling scheme, Stereo-Array Isotope Labeling (SAIL) method.
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