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Medicinal-Pharmaceutical Chemistry Commons™
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Full-Text Articles in Medicinal-Pharmaceutical Chemistry
Molecular Basis Of Substrate Recognition In Bjai, An Ahl Synthase From Bradyrhizobium Japonicum, Nicole Cornell
Molecular Basis Of Substrate Recognition In Bjai, An Ahl Synthase From Bradyrhizobium Japonicum, Nicole Cornell
Boise State University Theses and Dissertations
Resistance to antibiotics has become a major challenge in today’s society for treating bacterial infections. Inhibition of quorum sensing has a potential to be a non-antibiotic based therapeutic that could be used to fight these bacterial infections. Quorum sensing is a cell density dependent, intercellular communication mechanism that bacteria use to synchronize behavior such as virulence and resistance to antibiotics. If this switch from planktonic to communal behavior can be inhibited, the bacteria will be less virulent. One possible way to accomplish this is by inhibiting the enzymes that are responsible for making the quorum sensing signaling molecules in Gram-negative …
A Rational Design Of A Selective Inhibitor For Kv1.1 Channels Prevalent In Demyelinated Nerves That Improves Their Impaired Axonal Conduction, Ahmed Al-Sabi, Declan Daly, Patrick Hoefer, Gemma K. Kinsella, Charles Metais, Mark Pickering, Caroline Herron, Seshu Kumar Kaza, Kieran Nolan, J. Oliver Dolly
A Rational Design Of A Selective Inhibitor For Kv1.1 Channels Prevalent In Demyelinated Nerves That Improves Their Impaired Axonal Conduction, Ahmed Al-Sabi, Declan Daly, Patrick Hoefer, Gemma K. Kinsella, Charles Metais, Mark Pickering, Caroline Herron, Seshu Kumar Kaza, Kieran Nolan, J. Oliver Dolly
Articles
K+ channels containing Kv1.1 α subunits, which become prevalent at internodes in demyelinated axons, may underlie their dysfunctional conduction akin to muscle weakness in multiple sclerosis. Small inhibitors were sought with selectivity for the culpable hyper-polarizing K+ currents. Modeling of interactions with the extracellular pore in a Kv1.1-deduced structure identified diaryldi(2-pyrrolyl)methane as a suitable scaffold with optimized alkyl ammonium side chains. The resultant synthesized candidate [2,2′-((5,5′(di-p-topyldiaryldi(2-pyrrolyl)methane)bis(2,2′carbonyl)bis(azanediyl)) diethaneamine·2HCl] (8) selectively blocked Kv1.1 channels (IC50 ≈ 15 μM) recombinantly expressed in mammalian cells, induced a positive shift in the voltage dependency of K+ current activation, and slowed its kinetics. It …