Discovery and Synthesis of Hydroxy-l-Proline Blockers of the Neutral Amino Acid Transporters SLC1A4 (ASCT1) and SLC1A5 (ASCT2).

As a conformationally restricted amino acid, hydroxy-l-proline is a versatile scaffold for the synthesis of diverse multi-functionalized pyrrolidines for probing the ligand binding sites of biological targets. With the goal to develop new inhibitors of the widely expressed amino acid transporters SLC1A4 and SLC1A5 (also known as ASCT1 and ASCT2), we synthesized and functionally screened synthetic hydroxy-l-proline derivatives using electrophysiological and radiolabeled uptake methods against amino acid transporters from the SLC1, SLC7, and SLC38 solute carrier families. We have discovered a novel class of alkoxy hydroxy-pyrrolidine carboxylic acids (AHPCs) that act as selective high-affinity inhibitors of the SLC1 family neutral amino acid transporters SLC1A4 and SLC1A5.

Rationale, design, and protocol for a hybrid type 1 effectiveness-implementation trial of a proactive smoking cessation electronic visit for scalable delivery via primary care: the E-STOP trial.

Background: Cigarette smoking remains the leading cause of preventable disease and death in the United States. Primary care offers an ideal setting to reach adults who smoke cigarettes and improve uptake of evidence-based cessation treatment. Although U.

Remote Carbon Monoxide Capture via REDCap: Evaluation of an Integrated Mobile Application.

Introduction: To improve the feasibility of remote biochemical verification of smoking status, our team developed "COast," a mobile app integrated with REDCap that allows a research participant to complete self-report research assessments and provide a breath sample via the iCOQuit Smokerlyzer for the purposes of carbon monoxide (CO) testing. The aims of the present study were to examine (1) the validity of remote CO data capture using COast as compared to gold-standard approaches (salivary cotinine, stand-alone CO monitor) and (2) the feasibility of remote CO data capture using COast as applied to both daily and weekly CO collection schedules.

Methods: Participants (N = 143, 59% Female), including recently quit (n = 36) and current (n = 107) smokers, completed a baseline video session to capture validity data, and then were randomized to daily or weekly CO monitoring for a period of 1 month.

The Lateral Metalation of Isoxazolo[3,4-]pyridazinones towards Hit-to-Lead Development of Selective Positive Modulators of Metabotropic Glutamate Receptors.

Isoxazolo[3,4-] pyridazinones ([3,4-]s) were previously shown to have selective positive modulation at the metabotropic glutamate receptor (mGluR) Subtypes 2 and 4, with no functional cross-reactivity at mGluR, mGluR, or mGluR. Additional analogs were prepared to access more of the allosteric pocket and achieve higher binding affinity, as suggested by homology modeling. Two different sets of analogs were generated.