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GHB analogs confer neuroprotection through specific interaction with the CaMKIIα hub domain.
Leurs U, Klein AB, McSpadden ED, Griem-Krey N, Solbak SMØ, Houlton J, Villumsen IS, Vogensen SB, Hamborg L, Gauger SJ, Palmelund LB, Larsen ASG, Shehata MA, Kelstrup CD, Olsen JV, Bach A, Burnie RO, Kerr DS, Gowing EK, Teurlings SMW, Chi CC, Gee CL, Frølund B, Kornum BR, van Woerden GM, Clausen RP, Kuriyan J, Clarkson AN, Wellendorph P. Leurs U, et al. Among authors: hamborg l. Proc Natl Acad Sci U S A. 2021 Aug 3;118(31):e2108079118. doi: 10.1073/pnas.2108079118. Proc Natl Acad Sci U S A. 2021. PMID: 34330837 Free PMC article.
The arrhythmogenic N53I variant subtly changes the structure and dynamics in the calmodulin N-terminal domain, altering its interaction with the cardiac ryanodine receptor.
Holt C, Hamborg L, Lau K, Brohus M, Sørensen AB, Larsen KT, Sommer C, Van Petegem F, Overgaard MT, Wimmer R. Holt C, et al. Among authors: hamborg l. J Biol Chem. 2020 May 29;295(22):7620-7634. doi: 10.1074/jbc.RA120.013430. Epub 2020 Apr 21. J Biol Chem. 2020. PMID: 32317284 Free PMC article.
Exploring the NCS-382 Scaffold for CaMKIIα Modulation: Synthesis, Biochemical Pharmacology, and Biophysical Characterization of Ph-HTBA as a Novel High-Affinity Brain-Penetrant Stabilizer of the CaMKIIα Hub Domain.
Tian Y, Shehata MA, Gauger SJ, Veronesi C, Hamborg L, Thiesen L, Bruus-Jensen J, Royssen JS, Leurs U, Larsen ASG, Krall J, Solbak SMØ, Wellendorph P, Frølund B. Tian Y, et al. Among authors: hamborg l. J Med Chem. 2022 Nov 24;65(22):15066-15084. doi: 10.1021/acs.jmedchem.2c00805. Epub 2022 Nov 8. J Med Chem. 2022. PMID: 36346645