BMS-986189 (macrocyclic peptide PD-1/PD-L1 inhibitor)

Ac(1)-Tyr-N(Me)Ala-Asn-Pro-Dap-Leu-Hyp-Trp-Dab-Trp(EtO2H)(EtO2H)-N(Me)Nle-N(Me)Nle-Leu-Cys(1)-Gly-NH2 is a highly specialized synthetic peptide designed to facilitate advanced biochemical and molecular biology research. Characterized by the incorporation of non-standard amino acids, methylated residues, and unique side-chain modifications such as ethoxycarbonyl tryptophan and methyl norleucine, this peptide offers enhanced stability and novel conformational properties. The sequence's complexity and tailored structure make it particularly valuable for investigations requiring precise molecular mimicry, structure-activity relationship studies, and the exploration of peptide-protein interactions. Its design supports robust performance in a variety of experimental settings, ensuring reliability and reproducibility for scientists seeking to explore the frontiers of peptide science.

Peptide-Protein Interaction Studies: In the realm of protein research, Ac(1)-Tyr-N(Me)Ala-Asn-Pro-Dap-Leu-Hyp-Trp-Dab-Trp(EtO2H)(EtO2H)-N(Me)Nle-N(Me)Nle-Leu-Cys(1)-Gly-NH2 serves as a powerful tool for dissecting the intricacies of peptide-protein binding events. The incorporation of non-canonical amino acids and backbone modifications allows researchers to probe the specificity and affinity of interactions with target proteins, facilitating the mapping of binding sites and elucidation of interaction mechanisms. Its resistance to enzymatic degradation further enhances its utility in in vitro binding assays and pull-down experiments, enabling extended incubation times and more reliable data collection.

Receptor Ligand Discovery: As a model ligand, this peptide is instrumental in the discovery and characterization of novel receptor targets. The unique sequence modifications can be exploited to assess how structural variation influences receptor engagement and signaling. By systematically altering the peptide's structure, researchers can identify critical motifs responsible for biological activity, aiding in the rational design of new ligands with improved selectivity or potency. Its application in high-throughput screening platforms accelerates the identification of promising receptor-ligand pairs for further study.

Enzyme Substrate Profiling: The sequence complexity of Ac(1)-Tyr-N(Me)Ala-Asn-Pro-Dap-Leu-Hyp-Trp-Dab-Trp(EtO2H)(EtO2H)-N(Me)Nle-N(Me)Nle-Leu-Cys(1)-Gly-NH2 makes it an excellent candidate for enzyme substrate profiling. Researchers utilize this peptide to evaluate substrate specificity for a range of proteolytic enzymes, including those that recognize post-translational modifications or non-standard residues. By monitoring cleavage patterns and reaction kinetics, scientists gain valuable insights into enzyme selectivity, catalytic efficiency, and the impact of structural modifications on enzymatic processing.

Structural Biology and Conformational Analysis: The modified backbone and side chains present in this synthetic peptide render it suitable for NMR spectroscopy, circular dichroism, and crystallography studies aimed at understanding peptide folding and secondary structure formation. Its resistance to conformational changes under varying experimental conditions allows for detailed investigations into the effects of methylation, side-chain modifications, and sequence context on peptide stability and dynamics. Such studies contribute to the broader knowledge of peptide architecture and inform the design of more stable or bioactive analogs.

Peptide-Based Probe Development: Leveraging its unique sequence and chemical modifications, this peptide is frequently employed as a scaffold for the development of biochemical probes. Researchers attach fluorescent, affinity, or photoactivatable tags to the peptide, enabling the visualization, tracking, or crosslinking of biomolecular targets in complex mixtures or cellular extracts. Its enhanced stability and specificity make it ideal for use in challenging environments where conventional peptides might degrade or lose activity, thus expanding the toolkit available for molecular detection and interaction mapping.

Chemical Biology Toolkits: Within chemical biology, Ac(1)-Tyr-N(Me)Ala-Asn-Pro-Dap-Leu-Hyp-Trp-Dab-Trp(EtO2H)(EtO2H)-N(Me)Nle-N(Me)Nle-Leu-Cys(1)-Gly-NH2 serves as a versatile component in the assembly of custom peptide libraries, molecular scaffolds, and conjugates. Its structural diversity supports the generation of analogs for SAR studies, the creation of bifunctional reagents for target identification, and the exploration of peptide-based molecular switches. By integrating this peptide into broader chemical biology workflows, researchers can accelerate the discovery of new bioactive molecules and deepen their understanding of molecular recognition processes.

1. C-peptide and its C-terminal fragments improve erythrocyte deformability in type 1 diabetes patients

2. The effect of B-type allatostatin neuropeptides on crosstalk between the insect immune response and cold tolerance

3. Sex differences in oxidative stress level and antioxidative enzymes expression and activity in obese pre-diabetic elderly rats treated with metformin or liraglutide

4. High fat diet and GLP-1 drugs induce pancreatic injury in mice

5. Relatedness of antibodies to peptides containing homocitrulline or citrulline in patients with rheumatoid arthritis