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Liposome Click Membrane Permeability Assay for Identifying Permeable Peptides

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A Correction to this article was published on 05 April 2021

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Abstract

Purpose

To develop a novel, target agnostic liposome click membrane permeability assay (LCMPA) using liposome encapsulating copper free click reagent dibenzo cyclooctyne biotin (DBCO-Biotin) to conjugate azido modified peptides that may effectively translocate from extravesicular space into the liposome lumen.

Method

DBCO-Biotin liposomes were prepared with egg phosphatidylcholine and cholesterol by lipid film rehydration, freeze/thaw followed by extrusion. Size of DBCO-Biotin liposomes were characterized with dynamic light scattering.

Results

The permeable peptides representing energy independent mechanism of permeability showed higher biotinylation in LCMPA. Individual peptide permeability results from LCMPA correlated well with shifts in potency in cellular versus biochemical assays (i.e., cellular/ biochemical ratio) demonstrating quantitative correlation to intracellular barrier in intact cells.

Conclusion

The study provides a novel membrane permeability assay that has potential to evaluate energy independent transport of diverse peptides.

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Authors and Affiliations

  1. Merck & Co., Inc., West Point, Pennsylvania, 19486, USA

    Tanvi J. Desai, Joe R. Cannon & Jerome Hochman

  2. MSD International, 8 Biomedical Grove, #04-01/05 Neuros Building,, Singapore, 138665, Singapore

    Arun Chandramohan, Hung Yi Kristal Kaan, Ahmad Sadruddin & Anthony W. Partridge

  3. Merck & Co., Inc., Kenilworth, New Jersey, 07033, USA

    Bahanu Habulihaz & Raymond Evers

  4. Merck & Co., Inc., Boston, Massachusetts, 02115, USA

    Tomi K. Sawyer

  5. Institute of Chemical and Engineering Sciences (ICES), Agency for Science, Technology, and Research (A*STAR), 8 Biomedical Grove, #07 Neuros Building,, Singapore, 138665, Singapore

    Tsz Ying Yuen, Charles Johannes, Dawn Thean, Chris J. Brown & David P. Lane

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  1. Tanvi J. Desai
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  2. Bahanu Habulihaz
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Correspondence to Tanvi J. Desai or Jerome Hochman.

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The original online version of this article was revised to replace Fig. 1. with the correct figure.

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Desai, T.J., Habulihaz, B., Cannon, J.R. et al. Liposome Click Membrane Permeability Assay for Identifying Permeable Peptides. Pharm Res 38, 843–850 (2021). https://doi.org/10.1007/s11095-021-03005-z

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  • DOI: https://doi.org/10.1007/s11095-021-03005-z

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