Publications by authors named "A Porro"
Therapeutic drugs, whose bioactivity is hindered by a photoremovable cage, offer the advantage of spatiotemporal confinement of their action to the target diseased tissue with improved bioavailability and efficacy. Here, we have applied such an approach to ivabradine (IVA), a bradycardic agent indicated for angina pectoris and heart failure, acting as a specific HCN channel blocker. To overcome the side effects due to its poor discrimination among HCN channel subtypes (HCN1-4), we prepared a caged version of IVA linked to a photocleavable bromoquinolinylmethyl group (BHQ-IVA).
View Article and Find Full Text PDFArticle Synopsis
- - HCN1-4 channels are essential for regulating heart and brain cell activity, and their dysfunction can lead to serious health issues like epilepsy and chronic pain, highlighting the need for targeted treatments.
- - Researchers determined the cryo-EM structure of HCN4 in complex with ivabradine, showing that the drug binds within the channel's open pore and identifies key amino acids that play a role in this interaction.
- - The study finds that ivabradine blocks ion flow by electrostatic repulsion, a process similar to how certain other compounds work, providing new insights into how this drug affects channel activity.
Article Synopsis
- - Hailey-Hailey disease is a rare skin disorder that typically appears in adults, caused by a mutation in the ATP2C1 gene, leading to weak connections between skin cells, resulting in painful blistering and lesions primarily in flexible areas of the body.
- - The disease has no specific gender or racial preference, with its prevalence being approximately 1 in 50,000 people, and is characterized by an unpredictable course that includes periods of flare-ups and remissions often triggered by environmental factors like heat and friction.
- - Diagnosis relies on clinical examination and specific histopathological findings, with treatment focusing on alleviating symptoms through a variety of topical and systemic medications, although there is currently no cure and no well-established treatment protocols
Binding of cAMP to Hyperpolarization activated cyclic nucleotide gated (HCN) channels facilitates pore opening. It is unclear why the isolated cyclic nucleotide binding domain (CNBD) displays in vitro lower affinity for cAMP than the full-length channel in patch experiments. Here we show that HCN are endowed with an affinity switch for cAMP.
View Article and Find Full Text PDF