Cyclic diguanosine-monophosphate (c-di-GMP) is a bacterial signaling molecule that triggers a switch from motile to sessile bacterial lifestyles. This mechanism is of considerable pharmaceutical interest, since it is related to bacterial virulence, biofilm formation, and persistence of infection. Previously, c-di-GMP has been reported to display a rich polymorphism of various oligomeric forms at millimolar concentrations, which differ in base stacking and G-quartet interactions. Here, we have analyzed the equilibrium and exchange kinetics between these various forms by NMR spectroscopy. We find that the association of the monomer into a dimeric form is in fast exchange (
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College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea. Electronic address:
Alzheimer's disease (AD) is the most commonly occurring brain disorder, characterized by the accumulation of amyloid-β (Aβ) and tau, subsequently leading to neurocognitive decline. 3-Amino-1-propanesulfonic acid (TPS) and its prodrug, currently under clinical trial III, serve as promising therapeutic agents targeting Aβ pathology by specifically preventing monomer-to-oligomer formation. Inspired by the potency of TPS prodrug, we hypothesized that conjugating TPS with human serum albumin (HSA) could enhance brain delivery and synergistically inhibit Aβ aggregation in mild to moderate AD.
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