Webinar January 2024 – Dr. Walrant

On Wednesday, January 17, 2024, an online seminar on "Analyzing peptide/lipid interactions by affinity photocrosslinking coupled to MS" was held at 3.30 p.m. (CET).

The speaker was Assist.-Prof. Dr. Astrid Walrant from the Sorbonne University, Paris, France.

If you are interested in the slides of the presentation, please get in touch with us!

Abstract

Membrane active peptides is a large class of peptides that interact with cell membranes to exert their biological action. Amongst them, antimicrobial peptides (AMPs) kill bacteria by compromising their membrane integrity and cell-penetrating peptides (CPPs) cross membranes in a non-destructive way. To better understand the molecular mechanisms underlying their biological action, we finely analyze the interactions of membrane-active peptides with model lipid membranes using affinity photocrosslinking coupled to MS. Recently, we used a benzophenone-based analogue of the CPP Penetratin to investigate its lipidic binding partners. We showed that the intrinsic reactivity of benzophenone in lipid membranes can sometimes be misleading, especially when trying to identify lipid partners in complex mixtures but can also lead to interesting secondary reactions that can be exploited to obtain additional information, such as depth of insertion and membrane compacity [1].

Using this approach, we showed that Penetratin interacts preferentially with the negatively charged lipid phosphatidylinositol-4,5-bisphosphate (PIP2), even in the presence of other negatively charged lipids con┬şsistently with other experimental approaches such as calorimetry and NMR [1]. Quantification of internalization of Penetratin in cells where PIP2 is blocked revealed a role for this lipid in the uptake mechanism [2].

References

[1] Bechtella L, Kirschbaum C, Cosset M, Clodic G, Matheron L, Bolbach G, Sagan S, Walrant A, Sachon E: Benzophenone Photoreactivity in a Lipid Bilayer To Probe Peptide/Membrane Interactions: Simple System, Complex Information, Anal. Chem. 2019, 91, 9102-9110. PubMed

[2] Bechtella L, Chalouhi E, Mil├ín Rodr├şguez P, Cosset M, Ravault D, Illien F, Sagan S, Carlier L, Lequin O, Fuchs PFJ, Sachon E, Walrant A: Structural Bases for the Involvement of Phosphatidylinositol-4,5-bisphosphate in the Internalization of the Cell-Penetrating Peptide Penetratin, ACS Chem. Biol. 2022, 17, 1427-1439. PubMed

If you are interested in the slides of the presentation, please get in touch with us!