Manipulation of Transmembrane Transport by Synthetic K⁺ Ionophore Depsipeptides and Its Implications in Glucose‐Stimulated Insulin Secretion in β‐Cells

Abstract

The cyclic depsipeptide cereulide toxin it is a very well‐known potassium electrogenic ionophore particularly sensitive to pancreatic beta cells. The mechanistic details of its specific activity are unknown. Here, we describe a series of synthetic substituted cereulide potassium ionophores that cause impressive selective activation of glucose‐induced insulin secretion in a constitutive manner in rat insulinoma INS1E cells. Our study demonstrates that the different electroneutral K+ transport mechanism exhibited by the anionic mutant depsipeptides when compared with classical electrogenic cereulides can have an important impact of pharmacological value on glucose‐stimulated insulin secretion.

Natural-product-based fluorescent probes: recent advances and applications

“…12). 51 Further, the carboxylic ester anchoring group was placed at a sufficient distance to avoid potential competition for hydrogen bonds. Unlike 42 , analogue 43 with a ( S )-2-hydroxypentanedioic acid moiety acted as a K + transporter with lower membrane depolarization and stimulated glucose-induced insulin secretion in a constitutive manner by activating mitochondrial function in rat insulinoma INS1E cells.…”

Silica Nanoparticle/Fluorescent Dye Assembly Capable of Ultrasensitively Detecting Airborne Triacetone Triperoxide: Proof-of-Concept Detection of Improvised Explosive Devices in the Workroom

“…We synthesized a number of fluorogenic probes that were tested for several types of analytes. The synthesis was performed by using Suzuki reactions, following previous experiences in developing fluorogenic probes by carbon–carbon coupling chemistry. − The new fluorogenic probes are shown in Figure . The amino-protected naphthalimides showed an increase of fluorescence in mixtures of organic solvents with increasing amounts of water (AIE) that disappeared when the structures contained unprotected amino groups.…”

Recent Advances in Bioactive Artificial Ionophores

“…The antimalarial, antimicrobial, immunosuppressive, and cytotoxic activities of these compounds were well studied and recently they were recognized as a novel group of agents with pro-apoptotic anticancer properties. [26] In a seminal work by J. L. Sessler's group, the biological activities of the prodigiosin analogues, also known as prodigiosenes (16)(17)(18)(19) were introduced (Figure 7A-D). [27] The rate of transport could be correlated with the anticancer activity which was confirmed by cell proliferation assays with A549 human lung and PC3 human prostate cancer cells.…”

“…In 2019, Barboiu and co‐workers reported a new series of synthetically substituted cereulide K + ionophores (Figure 5 A). [19] Interestingly, substitution of one hydroxy acid i.e . the (S)‐2‐hydroxy‐3‐methylbutanoic acid, by ( S )‐2‐hydroxypentanedioic acid in the backbone structure of the synthetic cereulide 12 altered biological property significantly.…”