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Physical Sciences and Mathematics Commons

Open Access. Powered by Scholars. Published by Universities.®

Chemistry

2019

Selected Works

Metabolism

Articles 1 - 3 of 3

Full-Text Articles in Physical Sciences and Mathematics

Broadly Applicable Methodology For The Rapid And Dosable Small Molecule-Mediated Regulation Of Transcription Factors In Human Cells, M. D. Shoulders, L. M. Ryno, Christina B. Cooley, J. W. Kelly, R. L. Wiseman Jun 2019

Broadly Applicable Methodology For The Rapid And Dosable Small Molecule-Mediated Regulation Of Transcription Factors In Human Cells, M. D. Shoulders, L. M. Ryno, Christina B. Cooley, J. W. Kelly, R. L. Wiseman

Christina B Cooley

Direct and selective small molecule control of transcription factor activity is an appealing avenue for elucidating the cell biology mediated by transcriptional programs. However, pharmacologic tools to modulate transcription factor activity are scarce because transcription factors are not readily amenable to small molecule-mediated regulation. Moreover, existing genetic approaches to regulate transcription factors often lead to high nonphysiologic levels of transcriptional activation that significantly impair our ability to understand the functional implications of transcription factor activity. Herein, we demonstrate that small molecule-mediated conformational control of protein degradation is a generally applicable, chemical biological methodology to obtain small molecule-regulated transcription factors that …


Oligocarbonate Molecular Transporters: Oligomerization-Based Syntheses And Cell-Penetrating Studies, Christina B. Cooley, B. M. Trantow, F. Nederberg, M. K. Kiesewetter, J. L. Hedrick, R. M. Waymouth, P. A. Wender Jun 2019

Oligocarbonate Molecular Transporters: Oligomerization-Based Syntheses And Cell-Penetrating Studies, Christina B. Cooley, B. M. Trantow, F. Nederberg, M. K. Kiesewetter, J. L. Hedrick, R. M. Waymouth, P. A. Wender

Christina B Cooley

A new family of guanidinium-rich molecular transporters featuring a novel oligocarbonate backbone with 1,7-side chain spacing is described. Conjugates can be rapidly assembled irrespective of length in a one-step oligomerization strategy that can proceed with concomitant introduction of probes (or by analogy drugs). The new transporters exhibit excellent cellular entry as determined by flow cytometry and fluorescence microscopy, and the functionality of their drug delivery capabilities was confirmed by the delivery of the bioluminescent small molecule probe luciferin and turnover by its intracellular target enzyme.


Developmental Changes In Pedunculopontine Nucleus (Ppn) Neurons, T. Kobayashi, C. Good, J. Biedermann, Christina B. Cooley, R. D. Skinner, E. E. García-Rill Jun 2019

Developmental Changes In Pedunculopontine Nucleus (Ppn) Neurons, T. Kobayashi, C. Good, J. Biedermann, Christina B. Cooley, R. D. Skinner, E. E. García-Rill

Christina B Cooley

The developmental decrease in rapid-eye-movement (REM) sleep in man occurs between birth and after puberty. We hypothesize that if this decrease in REM sleep does not occur, lifelong increases in REM sleep drive may ensue. Such disorders are characterized by hypervigilance and sensory-gating deficits, such as are present in postpubertal onset disorders like schizophrenia, panic attacks (a form of anxiety disorder), and depression. The decrease in REM sleep in the rat occurs between 10 and 30 days of age. We studied changes in size and physiological properties of pedunculopontine nucleus (PPN) cells involved in the control of arousal, i.e., waking …