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Recombinant Synthesis of Hybrid Lipid-Peptide Polymer Fusions that Self-Assemble and Encapsulate Hydrophobic Drugs.

Publication ,  Journal Article
Luginbuhl, KM; Mozhdehi, D; Dzuricky, M; Yousefpour, P; Huang, FC; Mayne, NR; Buehne, KL; Chilkoti, A
Published in: Angewandte Chemie (International ed. in English)
November 2017

Inspired by biohybrid molecules that are synthesized in Nature through post-translational modification (PTM), we have exploited a eukaryotic PTM to recombinantly synthesize lipid-polypeptide hybrid materials. By co-expressing yeast N-myristoyltransferase with an elastin-like polypeptide (ELP) fused to a short recognition sequence in E. coli, we show robust and high-yield modification of the ELP with myristic acid. The ELP's reversible phase behavior is retained upon myristoylation and can be tuned to span a 30-60 °C. Myristoylated ELPs provide a versatile platform for genetically pre-programming self-assembly into micelles of varied size and shape. Their lipid cores can be loaded with hydrophobic small molecules by passive diffusion. Encapsulated doxorubicin and paclitaxel exhibit cytotoxic effects on 4T1 and PC3-luc cells, respectively, with potencies similar to chemically conjugated counterparts, and longer plasma circulation than free drug upon intravenous injection in mice.

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Published In

Angewandte Chemie (International ed. in English)

DOI

EISSN

1521-3773

ISSN

1433-7851

Publication Date

November 2017

Volume

56

Issue

45

Start / End Page

13979 / 13984

Related Subject Headings

  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Proof of Concept Study
  • Polymers
  • Pharmaceutical Preparations
  • Peptides
  • Paclitaxel
  • Organic Chemistry
  • Mice
  • Lipids
  • Hydrophobic and Hydrophilic Interactions
 

Citation

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Luginbuhl, K. M., Mozhdehi, D., Dzuricky, M., Yousefpour, P., Huang, F. C., Mayne, N. R., … Chilkoti, A. (2017). Recombinant Synthesis of Hybrid Lipid-Peptide Polymer Fusions that Self-Assemble and Encapsulate Hydrophobic Drugs. Angewandte Chemie (International Ed. in English), 56(45), 13979–13984. https://doi.org/10.1002/anie.201704625
Luginbuhl, Kelli M., Davoud Mozhdehi, Michael Dzuricky, Parisa Yousefpour, Fred C. Huang, Nicholas R. Mayne, Kristen L. Buehne, and Ashutosh Chilkoti. “Recombinant Synthesis of Hybrid Lipid-Peptide Polymer Fusions that Self-Assemble and Encapsulate Hydrophobic Drugs.Angewandte Chemie (International Ed. in English) 56, no. 45 (November 2017): 13979–84. https://doi.org/10.1002/anie.201704625.
Luginbuhl KM, Mozhdehi D, Dzuricky M, Yousefpour P, Huang FC, Mayne NR, et al. Recombinant Synthesis of Hybrid Lipid-Peptide Polymer Fusions that Self-Assemble and Encapsulate Hydrophobic Drugs. Angewandte Chemie (International ed in English). 2017 Nov;56(45):13979–84.
Luginbuhl, Kelli M., et al. “Recombinant Synthesis of Hybrid Lipid-Peptide Polymer Fusions that Self-Assemble and Encapsulate Hydrophobic Drugs.Angewandte Chemie (International Ed. in English), vol. 56, no. 45, Nov. 2017, pp. 13979–84. Epmc, doi:10.1002/anie.201704625.
Luginbuhl KM, Mozhdehi D, Dzuricky M, Yousefpour P, Huang FC, Mayne NR, Buehne KL, Chilkoti A. Recombinant Synthesis of Hybrid Lipid-Peptide Polymer Fusions that Self-Assemble and Encapsulate Hydrophobic Drugs. Angewandte Chemie (International ed in English). 2017 Nov;56(45):13979–13984.
Journal cover image

Published In

Angewandte Chemie (International ed. in English)

DOI

EISSN

1521-3773

ISSN

1433-7851

Publication Date

November 2017

Volume

56

Issue

45

Start / End Page

13979 / 13984

Related Subject Headings

  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Proof of Concept Study
  • Polymers
  • Pharmaceutical Preparations
  • Peptides
  • Paclitaxel
  • Organic Chemistry
  • Mice
  • Lipids
  • Hydrophobic and Hydrophilic Interactions