Self‐organization Properties of a GPCR‐Binding Peptide with a Fluorinated Tail Studied by Fluorine NMR Spectroscopy

Muizon, Capucine Jourdain de; Ramanoudjame, Sridévi M; Esteoulle, Lucie; Ling, Claude; Brou, Germain A.; Anton, Nicolas; Vandamme, Thierry F.; Delsuc, Marc-André; Bron, Dominique; Kieffer, Bruno

doi:10.1002/cbic.202000601

Cited by 5 publications

(2 citation statements)

References 29 publications

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“…Nanoscale biomolecular aggregates containing peptides or proteins have applications in a wide range of fields. Micelle, bicelle and nanodisc systems are used to characterize membrane proteins 1 , 2 , high and low-density lipoproteins (HDL and LDL) are lipid droplets with apolipoproteins attached on their surface 3 , 4 , and nanodiscs stabilized by apolipoprotein mimetic and peptide micelles have potential pharmaceutical applications 5 , 6 . However, these small and highly dynamic aggregates are inaccessible with most experimental methods that deliver atomistic resolution data of biomolecular systems, such as crystallography or electron microscopy.…”

Section: Introductionmentioning

confidence: 99%

Probing the dynamic landscape of peptides in molecular assemblies by synergized NMR experiments and MD simulations

Nencini,

Regnier,

Backlund

et al. 2024

Commun Chem

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Peptides or proteins containing small biomolecular aggregates, such as micelles, bicelles, droplets and nanodiscs, are pivotal in many fields ranging from structural biology to pharmaceutics. Monitoring dynamics of such systems has been limited by the lack of experimental methods that could directly detect their fast (picosecond to nanosecond) timescale dynamics. Spin relaxation times from NMR experiments are sensitive to such motions, but their interpretation for biomolecular aggregates is not straightforward. Here we show that the dynamic landscape of peptide-containing molecular assemblies can be determined by a synergistic combination of solution state NMR experiments and molecular dynamics (MD) simulations. Solution state NMR experiments are straightforward to implement without an excessive amount of sample, while direct combination of spin relaxation data to MD simulations enables interpretation of dynamic landscapes of peptides and other aggregated molecules. To demonstrate this, we interpret NMR data from transmembrane, peripheral, and tail anchored peptides embedded in micelles. Our results indicate that peptides and detergent molecules do not rotate together as a rigid body, but peptides rotate in a viscous medium composed of detergent micelle. Spin relaxation times also provide indirect information on peptide conformational ensembles. This work gives new perspectives on peptide dynamics in complex biomolecular assemblies.

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Section: Introductionmentioning

confidence: 99%

Probing the dynamic landscape of peptides in molecular assemblies by synergized NMR experiments and MD simulations

Nencini,

Regnier,

Backlund

et al. 2024

Commun Chem

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“…When incorporated in liposomes, pegylated apelin-13 could be efficiently delivered to endothelial cells in tumors, showing the potential of liposomes as a DDS to prolong apelin-like activity . The interaction mode of apelin-derived peptides with liposomes is still largely unknown, although NMR has been used previously to get detailed insight into the structure of apelin peptides, their molecular interactions with membrane models, and the self-aggregation properties of their various derivatives. − …”

Section: Introductionmentioning

confidence: 99%

Nuclear Magnetic Resonance Spectroscopy: A Multifaceted Toolbox to Probe Structure, Dynamics, Interactions, and Real-Time In Situ Release Kinetics in Peptide-Liposome Formulations

et al. 2021

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Liposomal formulations represent attractive biocompatible and tunable drug delivery systems for peptide drugs. Among the tools to analyze their physicochemical properties, nuclear magnetic resonance (NMR) spectroscopy, despite being an obligatory technique to characterize molecular structure and dynamics in chemistry as well as in structural biology, yet appears to be rather sparsely used to study drug-liposome formulations. In this work, we exploited several facets of liquid-state NMR spectroscopy to characterize liposomal delivery systems for the apelin-derived K14P peptide and K14P modified by Nα-fatty acylation. Various liposome compositions and preparation modes were analyzed. Using NMR, in combination with cryo-electron microscopy and dynamic light scattering, we determined structural, dynamic, and self-association properties of these peptides in solution and probed their interactions with liposomes. Using 31P and 1H NMR, we characterized membrane fluidity and thermotropic phase transitions in empty and loaded liposomes. Based on diffusion and 1H NMR experiments, we localized and quantified peptides with respect to the interior/exterior of liposomes and changes over time and upon thermal treatments. Finally, we assessed the release kinetics of several solutes and compared various formulations. Taken together, this work shows that NMR has the potential to assist the design of peptide/liposome systems and more generally drug delivery systems.

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Localized apelin-17 analogue-bicelle interactions as a facilitator of membrane-catalyzed receptor recognition and binding

Phạm,

Murza,

Marsault

et al. 2024

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Self‐organization Properties of a GPCR‐Binding Peptide with a Fluorinated Tail Studied by Fluorine NMR Spectroscopy

Cited by 5 publications

References 29 publications

Probing the dynamic landscape of peptides in molecular assemblies by synergized NMR experiments and MD simulations

Probing the dynamic landscape of peptides in molecular assemblies by synergized NMR experiments and MD simulations

Nuclear Magnetic Resonance Spectroscopy: A Multifaceted Toolbox to Probe Structure, Dynamics, Interactions, and Real-Time In Situ Release Kinetics in Peptide-Liposome Formulations

Localized apelin-17 analogue-bicelle interactions as a facilitator of membrane-catalyzed receptor recognition and binding

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