α-Conotoxins (α-CTxs) are structurally related peptides that antagonize nicotinic acetylcholine receptors (nAChRs), which may serve as new alternatives to opioid-based treatment for pain-related conditions. The non-natural amino acid analogues of α-CTxs have been demonstrated with improved potency compared to the native peptide. In this study, we chemically synthesized Dab/Dap-substituted analogues of α-CTx PeIA and evaluated their activity at heterologously expressed human α9α10 nAChRs. PeIA[S4Dap, S9Dap] had the most potent half-maximal inhibitory concentration (IC50) of 0.93 nM. Molecular dynamic simulations suggested that the side chain amino group of Dap4 formed additional hydrogen bonds with S168 and D169 of the receptor and Dap9 formed an extra hydrogen bond interaction with Q34, which is distinctive to PeIA. Overall, our findings provide new insights into further development of more potent analogues of α-CTxs, and PeIA[S4Dap, S9Dap] has potential as a drug candidate for
A new study from Tel Aviv University discovered that a known practice in information technology can also be applied to chemistry. Researchers found that to enhance the sampling in chemical simulat .
Solubilities and Self-Diffusion Coefficients of Light n-Alkanes in NaCl Solutions at the Temperature Range (278 15–308 15) K and Pressure Range (1–300) bar and Thermodynamics Properties of Their Corresponding Hydrates at (150–290) K and (1–7000) bar acs.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from acs.org Daily Mail and Mail on Sunday newspapers.
MyJournals.org - Science - [ASAP] Anisotropic and Finite Effects on Intermolecular Vibration and Relaxation Dynamics: Low-Frequency Raman Spectroscopy of Water Film and Droplet on Graphene by Molecular Dynamics Simulations (Journal of Physical Chemistry B)
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