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Conjugation of Amine-Functionalized Polyesters With Dimethylcasein Using Microbial Transglutaminase.

Abstract

Protein-polymer conjugates have been used as therapeutics because they exhibit frequently higher stability, prolonged in vivo half-life, and lower immunogenicity compared with native proteins. The first part of this report describes the enzymatic synthesis of poly(glycerol adipate) (PGA(M)) by transesterification between glycerol and dimethyl adipate using lipase B from Candida antarctica. PGA(M) is a hydrophilic, biodegradable but water insoluble polyester. By acylation, PGA(M) is modified with 6-(Fmoc-amino)hexanoic acid and with hydrophilic poly(ethylene glycol) side chains (mPEG12) rendering the polymer highly water soluble. This is followed by the removal of protecting groups, fluorenylmethyloxycarbonyl, to generate polyester with primary amine groups, namely PGA(M)-g-NH2-g-mPEG12. 1H NMR spectroscopy, FTIR spectroscopy, and gel permeation chromatography have been used to determine the chemical structure and polydispersity index of PGA(M) before and after modification. In the second part, we discuss the microbial transglutaminase-mediated conjugation of the model protein dimethylcasein with PGA(M)-g-NH2-g-mPEG12 under mild reaction conditions. SDS-PAGE proves the protein-polyester conjugation.

Authors+Show Affiliations

Department of Physical Chemistry, Institute of Chemistry, Martin Luther University Halle-Wittenberg, D-06099 Halle/Saale, Germany; Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, D-06120 Halle/Saale, Germany.Department of Physical Chemistry, Institute of Chemistry, Martin Luther University Halle-Wittenberg, D-06099 Halle/Saale, Germany.Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, D-06120 Halle/Saale, Germany.Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, D-06120 Halle/Saale, Germany. Electronic address: markus.pietzsch@pharmazie.uni-halle.de.Department of Physical Chemistry, Institute of Chemistry, Martin Luther University Halle-Wittenberg, D-06099 Halle/Saale, Germany. Electronic address: joerg.kressler@chemie.uni-halle.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31682828

Citation

Alaneed, Razan, et al. "Conjugation of Amine-Functionalized Polyesters With Dimethylcasein Using Microbial Transglutaminase." Journal of Pharmaceutical Sciences, 2019.
Alaneed R, Hauenschild T, Mäder K, et al. Conjugation of Amine-Functionalized Polyesters With Dimethylcasein Using Microbial Transglutaminase. J Pharm Sci. 2019.
Alaneed, R., Hauenschild, T., Mäder, K., Pietzsch, M., & Kressler, J. (2019). Conjugation of Amine-Functionalized Polyesters With Dimethylcasein Using Microbial Transglutaminase. Journal of Pharmaceutical Sciences, doi:10.1016/j.xphs.2019.10.052.
Alaneed R, et al. Conjugation of Amine-Functionalized Polyesters With Dimethylcasein Using Microbial Transglutaminase. J Pharm Sci. 2019 Nov 2; PubMed PMID: 31682828.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Conjugation of Amine-Functionalized Polyesters With Dimethylcasein Using Microbial Transglutaminase. AU - Alaneed,Razan, AU - Hauenschild,Till, AU - Mäder,Karsten, AU - Pietzsch,Markus, AU - Kressler,Jörg, Y1 - 2019/11/02/ PY - 2019/08/09/received PY - 2019/10/28/revised PY - 2019/10/28/accepted PY - 2019/11/5/pubmed PY - 2019/11/5/medline PY - 2019/11/5/entrez KW - CAL-B KW - amine-functionalized polyester KW - enzymatic polymerization KW - microbial transglutaminase (mTGase) KW - poly(glycerol adipate) (M) KW - protein-polymer conjugate JF - Journal of pharmaceutical sciences JO - J Pharm Sci N2 - Protein-polymer conjugates have been used as therapeutics because they exhibit frequently higher stability, prolonged in vivo half-life, and lower immunogenicity compared with native proteins. The first part of this report describes the enzymatic synthesis of poly(glycerol adipate) (PGA(M)) by transesterification between glycerol and dimethyl adipate using lipase B from Candida antarctica. PGA(M) is a hydrophilic, biodegradable but water insoluble polyester. By acylation, PGA(M) is modified with 6-(Fmoc-amino)hexanoic acid and with hydrophilic poly(ethylene glycol) side chains (mPEG12) rendering the polymer highly water soluble. This is followed by the removal of protecting groups, fluorenylmethyloxycarbonyl, to generate polyester with primary amine groups, namely PGA(M)-g-NH2-g-mPEG12. 1H NMR spectroscopy, FTIR spectroscopy, and gel permeation chromatography have been used to determine the chemical structure and polydispersity index of PGA(M) before and after modification. In the second part, we discuss the microbial transglutaminase-mediated conjugation of the model protein dimethylcasein with PGA(M)-g-NH2-g-mPEG12 under mild reaction conditions. SDS-PAGE proves the protein-polyester conjugation. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/31682828/Conjugation_of_Amine_Functionalized_Polyesters_with_Dimethylcasein_Using_Microbial_Transglutaminase_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(19)30723-3 DB - PRIME DP - Unbound Medicine ER -