Recombinant Synthesis of Hybrid Lipid–Peptide Polymer Fusions that Self‐Assemble and Encapsulate Hydrophobic Drugs
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...
Saved in:
Published in | Angewandte Chemie International Edition Vol. 56; no. 45; pp. 13979 - 13984 |
---|---|
Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Germany
Wiley Subscription Services, Inc
06.11.2017
|
Edition | International ed. in English |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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.
Inspired by nature: By introducing an enzyme that carries out myristoylation, a eukaryotic post‐translational modification, into E. coli, recombinant synthesis of lipid–peptide polymer hybrid materials at high yield is demonstrated. Myristoylated micelles loaded with anti‐cancer drugs are cytotoxic towards cancer cell lines and exhibit a much longer plasma half‐life than free drug. |
---|---|
Bibliography: | These authors contributed equally to this work. |
ISSN: | 1433-7851 1521-3773 |
DOI: | 10.1002/anie.201704625 |