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Keeping dry and crossing membranes

Nature Biotechnology volume 22, pages 1081–1084 (2004)Cite this article

Water sustains life but also imposes constraints on what life should be like. Its high dipole moment, proton donor-acceptor dual nature and rotational freedom make it a powerful former of hydrogen bonds. In soluble proteins, this property places stringent constraints on the way proteins interact1,2,3,4 and fold5. I argue here that the manipulation of intramolecularly underdehydrated or underwrapped electrostatic interactions in proteins can be exploited in engineering strategies to create molecules with an enhanced ability to traverse biological membranes, with potential implications for oral delivery of peptide-based drugs.

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Figure 1: Wrapping of the glucagon molecule in helical conformation (PDB entry 1GCN).
Figure 2: Time dependence of the adsorption uptake and desorption of soluble mutants of the G4V glucagon peptide onto and from a dilauryl phosphatidylcholine bilayer coating a biosensing optical device.

Bob Crimi

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Acknowledgements

This research was supported in part by an unrestricted grant from Eli Lilly and Company. The work was motivated by conversations with Richard DiMarchi.

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Authors and Affiliations

  1. Indiana University School of Informatics and Center for Computational Biology and Bioinformatics, Indiana University Medical School, 714 N. Senate Avenue, Indianapolis, 46202, Indiana, USA

    Ariel Fernández

  2. Department of Computer Science, The University of Chicago, Chicago, 60637, Illinois, USA

    Ariel Fernández

  3. Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka, 565-0871, Japan

    Ariel Fernández

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Fernández, A. Keeping dry and crossing membranes. Nat Biotechnol 22, 1081–1084 (2004). https://doi.org/10.1038/nbt0904-1081

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