834 research outputs found

    Diversity-Oriented Enzymatic Synthesis of Cyclopropane Building Blocks

    Get PDF
    While biocatalysis is increasingly incorporated into drug development pipelines, it is less commonly used in the early stages of drug discovery. By engineering a protein to produce a chiral motif with a derivatizable functional handle, biocatalysts can be used to help generate diverse building blocks for drug discovery. Here we show the engineering of two variants of Rhodothermus marinus nitric oxide dioxygenase (RmaNOD) to catalyze the formation of cis- and trans-diastereomers of a pinacolboronate-substituted cyclopropane which can be readily derivatized to generate diverse stereopure cyclopropane building blocks

    Diversity-Oriented Enzymatic Synthesis of Cyclopropane Building Blocks

    Get PDF
    While biocatalysis is increasingly incorporated into drug development pipelines, it is less commonly used in the early stages of drug discovery. By engineering a protein to produce a chiral motif with a derivatizable functional handle, biocatalysts can be used to help generate diverse building blocks for drug discovery. Here we show the engineering of two variants of Rhodothermus marinus nitric oxide dioxygenase (RmaNOD) to catalyze the formation of cis- and trans-diastereomers of a pinacolboronate-substituted cyclopropane which can be readily derivatized to generate diverse stereopure cyclopropane building blocks

    Trajectories of Quality of Life after Hematopoietic Cell Transplantation: Secondary Analysis of BMT CTN 0902 Data

    Get PDF
    Quality of life is increasingly recognized as an important secondary endpoint of hematopoietic cell transplantation (HCT). The current study examined the extent to which attrition results in biased estimates of patient quality of life. The study also examined whether patients differ in terms of trajectories of quality of life in the first six months post-transplant. A secondary data analysis was conducted of 701 participants who enrolled in the Blood and Marrow Transplantation Clinical Trials Network (BMT CTN) 0902 trial. Participants completed the SF-36, a measure of quality of life, prior to transplant and 100 and 180 days post-transplant. Results indicated that attrition resulted in slightly biased overestimates of quality of life but the amount of overestimation remained stable over time. Patients could be grouped into three distinct classes based on physical quality of life: 1) low and stable; 2) average and declining, then stable; and 3) average and stable. Four classes of patients emerged for mental quality of life: 1) low and stable; 2) average, improving, then stable; 3) higher than average (by almost 1 SD) and stable; and 4) average and stable. Taken together, these data provide a more comprehensive understanding of quality of life that can be used to educate HCT recipients and their caregivers
    • …
    corecore