Ion Channels and Transporters as Therapeutic Agents: From Biomolecules to Supramolecular Medicinal Chemistry

Abstract

Ion channels and transporters typically consist of biomolecules that play key roles in a large variety of physiological and pathological processes. Traditional therapies include many ion-channel blockers, and some activators, although the exact biochemical pathways and mechanisms that regulate ion homeostasis are yet to be fully elucidated. An emerging area of research with great innovative potential in biomedicine pertains the design and development of synthetic ion channels and transporters, which may provide unexplored therapeutic opportunities. However, most studies in this challenging and multidisciplinary area are still at a fundamental level. In this review, we discuss the progress that has been made over the last five years on ion channels and transporters, touching upon biomolecules and synthetic supramolecules that are relevant to biological use. We conclude with the identification of therapeutic opportunities for future exploration.

Dipeptide self-assembly into water-channels and gel biomaterial

“…This finding is of potential interest to develop supramolecular channels that mediate selective transport of guests through membranes; this is becoming a hot topic for innovative therapies to target diseases as diverse as channelopathies and chronic pain. 43 Besides ion-channels, also watertransport is attracting interest as demonstrated by aquaporin mimicry research for desalination and purification. 44 Further, the presence of water molecules mediating peptide-peptide interactions appears as a distinctive feature of non-gelling dipeptides, as previously found for tripeptides.…”

Nanotubes and water-channels from self-assembling dipeptides

“…161 The control of NT growth for potential insertions into membranes could clearly open up new avenues, for instance to alter transport of guests selectively and find new means for therapeutic treatment. 162 Amongst the various approaches to control NT length, microfluidics is emerging as one possible strategy. 163 Alternatively, gases could be envisaged as channel guests, and one study appeared showing that porous dipeptide crystals have a remarkable selectivity for methane, carbon dioxide, and hydrogen absorption.…”

Discriminating Ion Channels from Non-Ion Channel Membrane Proteins Using Machine Learning and Deep Learning Classifiers with Protein Language Model Representations

“…As such, ion channels have garnered significant attention in the field of membrane protein research, with extensive studies focused on their structure, function, and regulation [4,5]. In the realm of drug discovery, ion channels represent promising targets for therapeutic intervention, as their modulation can result in changes in cellular behavior [6,7]. However, the high cost and time required for wet lab experiments to characterize ion channels has spurred the development of computational methods for this purpose [8,9].…”