The Plasma Membrane as a Reservoir, Protective Shield, and Light-Triggered Launch Pad for Peptide Therapeutics
Colin P. O'Banion
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599 USA
Search for more papers by this authorDr. Luong T. Nguyen
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599 USA
Search for more papers by this authorProf. Qunzhao Wang
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599 USA
Search for more papers by this authorProf. Melanie A. Priestman
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599 USA
Search for more papers by this authorProf. Stephen P. Holly
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, 27599 USA
Search for more papers by this authorProf. Leslie V. Parise
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, 27599 USA
Search for more papers by this authorCorresponding Author
Prof. David S. Lawrence
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599 USA
Search for more papers by this authorColin P. O'Banion
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599 USA
Search for more papers by this authorDr. Luong T. Nguyen
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599 USA
Search for more papers by this authorProf. Qunzhao Wang
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599 USA
Search for more papers by this authorProf. Melanie A. Priestman
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599 USA
Search for more papers by this authorProf. Stephen P. Holly
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, 27599 USA
Search for more papers by this authorProf. Leslie V. Parise
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, 27599 USA
Search for more papers by this authorCorresponding Author
Prof. David S. Lawrence
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599 USA
Search for more papers by this authorAbstract
Although peptide-based therapeutics are finding increasing application in the clinic, extensive structural modification is typically required to prevent their rapid degradation by proteases in the blood. We have evaluated the ability of erythrocytes to serve as reservoirs, protective shields (against proteases), and light-triggered launch pads for peptides. We designed lipidated peptides that are anchored to the surface of red blood cells, which furnishes a protease-resistant environment. A photocleavable moiety is inserted between the lipid anchor and the peptide backbone, thereby enabling light-triggered peptide release from erythrocytes. We have shown that a cell-permeable peptide, a hormone (melanocyte stimulating hormone), and a blood-clotting agent can be anchored to erythrocytes, protected from proteases, and photolytically released to create the desired biological effect.
Supporting Information
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
| Filename | Description |
|---|---|
| ange201508767-sup-0001-misc_information.pdf4.3 MB | Supplementary |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1K. Fosgerau, T. Hoffmann, Drug Discovery Today 2014, 19, 122–128.
- 2
- 2aG. L. Verdine, G. J. Hilinski, Methods Enzymol. 2012, 503, 3–33;
- 2bA. Adamska, A. Janecka, Curr. Med. Chem. 2015, 22, 352–359.
- 3A. A. Kaspar, J. M. Reichert, Drug Discovery Today 2013, 18, 807–817.
- 4S. Srivastava, S. R. Riddell, Trends Immunol. 2015, 36, 494–502.
- 5
- 5aV. R. Muzykantov, Expert Opin. Drug Delivery 2010, 7, 403–427;
- 5bJ. R. Bagó, K. T. Sheets, S. D. Hingtgen, Methods 2015, S1046–2023, 30059–1.
- 6L. T. Nguyen, N. P. Oien, N. L. Allbritton, D. S. Lawrence, Angew. Chem. Int. Ed. 2013, 52, 9936–9939; Angew. Chem. 2013, 125, 10120–10123.
- 7
- 7aS. J. Getting, M. Kaneva, Y. Bhadresa, D. Renshaw, G. Leoni, H. B. Patel, P. M. Kerrigan, I. C. Locke, Scientific World J. 2009, 9, 1394–1414;
- 7bT. A. Luger, T. Brzoska, Ann. Rheum. Dis. 2007, 66, 52–55.
- 8
- 8aM. Böhm, S. Grässel, Endocr. Rev. 2012, 33, 623–651;
- 8bA. Catania, S. Gatti, G. Colombo, J. M. Lipton, Pharmacol. Rev. 2004, 56, 1–29.
- 9Z. A. Abdel-Malek, V. B. Swope, R. J. Starner, L. Koikov, P. Cassidy, S. Leachman, Arch. Biochem. Biophys. 2014, 563, 4–12.
- 10
- 10aR. R. Vassallo, T. Kieber-Emmons, K. Cichowski, L. F. Brass, J. Biol. Chem. 1992, 267, 6081–6085;
- 10bH. Andersen, D. L. Greenberg, K. Fujikawa, W. Xu, D. W. Chung, E. W. Davie, Proc. Natl. Acad. Sci. USA 1999, 96, 11189–11193.
- 11D. M. Feng, D. F. Veber, T. M. Connolly, C. Condra, M. J. Tang, R. F. Nutt, J. Med. Chem. 1995, 38, 4125–4130.
- 12S. P. Holly, J. W. Chang, W. Li, S. Niessen, R. M. Phillips, R. Piatt, J. L. Black, M. C. Smith, Y. Boulaftali, A. S. Weyrich, W. Bergmeier, B. F. Cravatt, L. V. Parise, Chem. Biol. 2013, 20, 1125–1134.
- 13D. Sadava, H. C. Heller, G. H. Orians, W. K. Purves, D. M. Hillis, Life: The Science of Biology, 7th ed., Sinauer Associates, Sunderland, 2006, p. 954). ISBN: 0-7167-9856-9855.
- 14
- 14aT. A. Shell, J. R. Shell, Z. L. Rodgers, D. S. Lawrence, Angew. Chem. Int. Ed. 2014, 53, 875–878; Angew. Chem. 2014, 126, 894–897;
- 14bW. J. Smith, N. P. Oien, R. M. Hughes, C. M. Marvin, Z. L. Rodgers, J. Lee, D. S. Lawrence, Angew. Chem. Int. Ed. 2014, 53, 10945–10948; Angew. Chem. 2014, 126, 11125–11128;
- 14cA. P. Gorka, R. R. Nani, J. J. Zhu, S. Machem, M. J. Schnermann, J. Am. Chem. Soc. 2014, 136, 14153–14159;
- 14dN. Rubinstein, P. Liu, E. W. Miller, R. Weinstain, Chem. Commun. 2015, 51, 6369–6372;
- 14eP. P. Goswami, A. Syed, C. L. Beck, T. R. Albright, K. M. Mahoney, R. Unash, E. A. Smith, A. H. Winter, J. Am. Chem. Soc. 2015, 137, 3783–3786.
Citing Literature
This is the
German version
of Angewandte Chemie.
Note for articles published since 1962:
Do not cite this version alone.
Take me to the International Edition version with citable page numbers, DOI, and citation export.
We apologize for the inconvenience.
