Immobilized thermolysin for highly efficient production of low‐molecular‐weight protamine—An attractive cell‐penetrating peptide for macromolecular drug delivery applications
dc.contributor.author | David, Allan E. | en_US |
dc.contributor.author | Gong, Junbo | en_US |
dc.contributor.author | Chertok, Beata | en_US |
dc.contributor.author | Domszy, Roman C. | en_US |
dc.contributor.author | Moon, Cheol | en_US |
dc.contributor.author | Park, Yoon Shin | en_US |
dc.contributor.author | Wang, Nam Sun | en_US |
dc.contributor.author | Yang, Arthur J. | en_US |
dc.contributor.author | Yang, Victor C. | en_US |
dc.date.accessioned | 2011-12-05T18:34:41Z | |
dc.date.available | 2013-03-04T15:29:55Z | en_US |
dc.date.issued | 2012-01 | en_US |
dc.identifier.citation | David, Allan E.; Gong, Junbo; Chertok, Beata; Domszy, Roman C.; Moon, Cheol; Park, Yoon Shin; Wang, Nam Sun; Yang, Arthur J.; Yang, Victor C. (2012). "Immobilized thermolysin for highly efficient production of low‐molecular‐weight protamine—An attractive cell‐penetrating peptide for macromolecular drug delivery applications ." Journal of Biomedical Materials Research Part A 100A(1): 211-219. <http://hdl.handle.net/2027.42/88093> | en_US |
dc.identifier.issn | 1549-3296 | en_US |
dc.identifier.issn | 1552-4965 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/88093 | |
dc.description.abstract | Macromolecules present a remarkable potential as future therapeutics. However, their translation into clinical practice has been hampered by an inherently low bioavailability. Cell‐penetrating peptides (CPP) have been recently shown to significantly improve on the bioavailability of macromolecules. Yet, the high cost associated with development and production of these peptides is a major factor hindering their rapid deployment beyond the laboratory. Here, we describe a facile and robust methodology for efficient and large‐scale production of low‐molecular‐weight protamine—a potent CPP of great clinical potential. Our methodology is based on the immobilization of thermolysin, an enzyme catalyzing digestion of native protamine, on chemically surface‐modified gels produced by silica sol–gel chemistry. Thermolysin was immobilized at extremely high matrix loading of 733 mg/g matrix and exhibited good thermal and pH stability, indicating robustness with respect to processing conditions. The mechanical properties of the silica matrix further allowed utilization of the immobilized thermolysin in both batch and packed‐bed reactor systems to produce the LMWP peptide in high yields. Results presented here are of high significance as this efficient and cost‐effective production of high purity LMWP could enable clinical translation of many potential macromolecular drugs. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012. | en_US |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Enzyme Immobilization | en_US |
dc.subject.other | Sol–Gel Silica | en_US |
dc.subject.other | Thermolysin | en_US |
dc.subject.other | Peptide Synthesis | en_US |
dc.subject.other | Protamine | en_US |
dc.subject.other | LMWP | en_US |
dc.subject.other | Cell‐Penetrating Peptide | en_US |
dc.title | Immobilized thermolysin for highly efficient production of low‐molecular‐weight protamine—An attractive cell‐penetrating peptide for macromolecular drug delivery applications | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Biomedical Engineering | en_US |
dc.subject.hlbtoplevel | Engineering | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Pharmaceutical Science, University of Michigan, Ann Arbor, Michigan 48109 | en_US |
dc.contributor.affiliationum | Department of Pharmaceutical Science, University of Michigan, Ann Arbor, Michigan 48109 | en_US |
dc.contributor.affiliationother | Department of Chemical Engineering, A. James Clark School of Engineering, University of Maryland, College Park, Maryland 20742 | en_US |
dc.contributor.affiliationother | Industrial Science & Technology Network (ISTN) Inc., York, Pennsylvania 17404 | en_US |
dc.contributor.affiliationother | Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China | en_US |
dc.contributor.affiliationother | Industrial Science & Technology Network (ISTN) Inc., York, Pennsylvania 17404 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/88093/1/33244_ftp.pdf | |
dc.identifier.doi | 10.1002/jbm.a.33244 | en_US |
dc.identifier.source | Journal of Biomedical Materials Research Part A | en_US |
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dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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