Structure Of PD-1 Research Articles

Structure-Guided Discovery of PD-1/PD-L1 Interaction Inhibitors: Peptide Design, Screening, and Optimization via Computation-Aided Phage Display Engineering.

Cancer immunotherapy harnesses the immune system to combat tumors and has emerged as a major cancer treatment modality. The PD-1/PD-L1 immune checkpoint modulates interactions between tumor cells and T cells and has been extensively targeted in cancer immunotherapy. However, the monoclonal antibodies known to target this immune checkpoint have considerable side effects, and novel PD-1/PD-L1 inhibitors are therefore required. Herein, a peptide inhibitor to disrupt PD-1/PD-L1 interactions was designed through structure-driven phage display engineering coupled to computational modification and optimization. BetaPb, a novel peptide library constructed by using the known structure of PD-1/PD-L, was used to develop inhibitors against the immune checkpoint, and specific peptides with high affinity toward PD-1 were screened through enzyme-linked immunosorbent assays, homogeneous time-resolved fluorescence, and biolayer interferometry. A potential inhibitor, B8, was preliminarily screened through biopanning. The binding affinity of B8 toward PD-1 was confirmed through computation-aided optimization. Assessment of B8 variants (B8.1, B8.2, B8.3, B8.4, and B8.5) demonstrated their attenuation of PD-1/PD-L1 interactions. B8.4 exhibited the strongest attenuation efficiency at a half-maximal effective concentration of 0.1 μM and the strongest binding affinity to PD-1 (equilibrium dissociation constant = 0.1 μM). B8.4 outperformed the known PD-1/PD-L1 interaction inhibitor PL120131 in disrupting PD-1/PD-L1 interactions, revealing that B8.4 has remarkable potential for modification to yield an antitumor agent. This study provides valuable information for the future development of peptide-based drugs, therapeutics, and immunotherapies for cancer.

Structure of PD1 and its mechanism in the treatment of autoimmune diseases.

PD-1 and CTLA-4 can play an important role in addressing the issue of autoimmune diseases. PD-1 is a transmembrane glycoprotein expressed on T, B, and Dentric cells. This molecule functions as a checkpoint in T cell proliferation. Ligation of PD-1 with its ligands inhibits the production of IL-2, IL-7, IL-10, and IL-12 as well as other cytokines by macrophages, natural killer (NK) cells, and T cells, which can suppress cell proliferation and inflammation. Today, scientists attempt to protect against autoimmune diseases by PD-1 inhibitory signals. In this review, we discuss the structure, expression, and signaling pathway of PD-1. In addition, we discuss the importance of PD-1 in regulating several autoimmune diseases, reflecting how manipulating this molecule can be an effective method in the immunotherapy of some autoimmune diseases.

Structures of pseudo-decagonal approximants in Al−Co−Ni

Quasi-crystals shocked the crystallographic world when they were reported in 1984. We now know that they are not a rare exception, and can be found in many alloy systems. One of the richer systems for quasi-crystals and their approximants is Al-Co-Ni. A large series of pseudo-decagonal (PD) approximants have been found. Only two of them, PD4 and PD8, have been solved by X-ray crystallography. We report here the structures of PD1, PD2, PD3 and PD5, solved from the limited information that is provided by electron diffraction patterns, unit cell dimensions and high-resolution electron microscopy images.

Antiferromagnetic spin correlations in palladium-based Pd-Fe, Pd-Fe-Ag, and Pd-Fe-Rh magnetic alloys

The magnetic structure of Pd1−x Fex (x=0.03, 0.06, 0.10, 0.15, and 0.20) alloys is investigated using the method of 57Fe-Mossbauer spectroscopy. The distribution functions P(B hf) of hyperfine magnetic fields have a discrete structure defined by variations of the contribution to B hf from the magnetic moment of the neighboring Fe atoms. The anomalies of intensities of components of the functions P(B hf), which increase with the concentration of iron, are indicative of the instability of configurations with a large total spin and of the formation of local spin configurations with the antiferromagnetic orientation of magnetic moments. The probability of formation of such configurations is defined by the competition of the ferromagnetic Fe-Pd exchange interaction with the direct antiferromagnetic exchange between the nearest neighboring atoms of Fe. An Ag or Rh impurity effectively induces the process of spin flipping, which explains the anomalously strong effect of impurities on the magnetic ordering temperature. The results confirm the presence in Pd-Fe alloys of perturbations of long-range ferromagnetic order revealed by neutron diffraction.

Examination of the Electronic Structure of Pd1−xNix Alloys by Positron Annihilation

The entire concentration range of α-phase Pd1−xNix alloys is studied by angular correlation of the positron annihilation radiation method at room temperature and at 90 K. The number of nearly free and d-itinerant electrons as well as interstitial electron density against x are calculated. The increase in d-itinerant electron number at low temperature as compared to room temperature results is possible to be the reason of the onset of ferromagnetism for the alloys with x ≦ 0.20. The electron redistribution model valid for Pd-noble metal alloys is not confirmed for PdNi alloys. The big difference in interstitial electron densities for Pd and Ni is consistent with “common-band” structure of PdNi alloys. Bei Raumtemperatur und 90 K wird der gesamte Konzentrationsbereich der α-Phasen-Pd1−xNix-Legierungen mittels Winkelkorrelationsmethode der Positronenannihilationsstrahlung untersucht. Sowohl die Zahl der fast freien und itineranten d-Elektronen als auch die Zwischengitterelektronendichte uber x werden berechnet. Das Anwachsen der Anzahl der itineranten d-Elektronen bei tiefen Temperaturen im Vergleich zu Raumtemperaturergebnissen ist moglicherweise der Grund des Einsetzens von Ferromagnetismus fur die Legierungen mit x = 0,20. Das fur Pd-Edelmetallegierungen gultige Modell der Elektronenverteilung wird fur PdNi-Legierungen nicht bestatigt. Die grose Differenz in den Zwischengitterelektronendichten fur Pd und Ni ist konsistent mit der „ublichen Band”-Struktur der PdNi-Legierungen.