A Chemical Biological Approach to Study G Protein-Coupled Receptors: Labeling the Adenosine A1 Receptor Using an Electrophilic Covalent Probe.

G protein-coupled receptors (GPCRs) have been known for decades as attractive drug targets. This has led to the development and approval of many ligands targeting GPCRs. Although ligand binding effects have been studied thoroughly for many GPCRs, there are multiple aspects of GPCR signaling that remain poorly understood. The reasons for this are the difficulties that are encountered upon studying GPCRs, for example, a poor solubility and low expression levels. In this work, we have managed to overcome some of these issues by developing an affinity-based probe for a prototypic GPCR, the adenosine A1 receptor (A1AR). Here, we show the design, synthesis, and biological evaluation of this probe in various biochemical assays, such as SDS-PAGE, confocal microscopy, and chemical proteomics.

What Are the Most Effective Factors in Determining Future Exacerbations, Morbidity Weight, and Mortality in Patients with COPD Attack?

BACKGROUND AND OBJECTIVES: This study aimed to investigate the important factors that affect COPD prognosis. MATERIALS AND METHODS: We included 160 hospitalized patients with COPD exacerbation in the study. The hemoglobin (HB), hematocrit (HCT), leukocytes, red cell distribution width (RDW), mean platelet volume, platelet distribution width, plateletcrits, platelets, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, eosinophils, uric acid, albumin, C-reactive protein (CRP), procalcitonin, arterial blood gases (PO2 and PCO2), pulmonary function test (FEV1 and FVC), echocardiography (ejection fraction-EF), Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, Modified Medical Research Council (mMRC) and Borg scales, Charlson comorbidity index, body mass index (BMI), and the length of hospital stay were examined on the first day of hospitalization. Admission to the hospital with a new attack, hospitalization in the intensive care unit (ICU), and mortality during the six months after discharge were evaluated. RESULTS: High CRP and procalcitonin levels were observed in the group with a long hospital stay. In the mortality group, the HB, HCT, BMI, and PO2 values were significantly lower than in the group without mortality, while the age and GOLD stage were higher. The age, Borg and mMRC scores, number of exacerbations experienced in the previous year, RDW, eosinophil count, and PCO2 were significantly higher in the ICU group than that without an ICU stay. The HCT and EF values were lower in the ICU group than that without an ICU stay. The FEV1 and FVC values were significantly lower in the follow-up attack group than those without a follow-up attack. The duration of COPD and the number of attacks that were experienced in the previous year were high. CONCLUSION: Scoring combining selected biomarkers and other factors is a strong determinant of the prognosis.