Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ymgme.2009.09.002
DC FieldValue
dc.titleConverting an injectable protein therapeutic into an oral form: Phenylalanine ammonia lyase for phenylketonuria
dc.contributor.authorKang, T.S.
dc.contributor.authorWang, L.
dc.contributor.authorSarkissian, C.N.
dc.contributor.authorGámez, A.
dc.contributor.authorScriver, C.R.
dc.contributor.authorStevens, R.C.
dc.date.accessioned2014-10-29T01:50:36Z
dc.date.available2014-10-29T01:50:36Z
dc.date.issued2010-01
dc.identifier.citationKang, T.S., Wang, L., Sarkissian, C.N., Gámez, A., Scriver, C.R., Stevens, R.C. (2010-01). Converting an injectable protein therapeutic into an oral form: Phenylalanine ammonia lyase for phenylketonuria. Molecular Genetics and Metabolism 99 (1) : 4-9. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ymgme.2009.09.002
dc.identifier.issn10967192
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/105778
dc.description.abstractPhenylalanine ammonia lyase (PAL) has long been recognized as a potential enzyme replacement therapeutic for treatment of phenylketonuria. However, various strategies for the oral delivery of PAL have been complicated by the low intestinal pH, aggressive proteolytic digestion and circulation time in the GI tract. In this work, we report 3 strategies to address these challenges. First, we used site-directed mutagenesis of a chymotrypsin cleavage site to modestly improve protease resistance; second, we used silica sol-gel material as a matrix to demonstrate that a silica matrix can provide protection to entrapped PAL proteins against intestinal proteases, as well as a low pH of 3.5; finally, we demonstrated that PEGylation of AvPAL surface lysines can reduce the inactivation of the enzyme by trypsin. © 2009 Elsevier Inc. All rights reserved.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.ymgme.2009.09.002
dc.sourceScopus
dc.subjectEnzyme substitution therapy
dc.subjectMetabolic disorder
dc.subjectPhenylketonuria
dc.subjectTherapeutic development
dc.typeArticle
dc.contributor.departmentPHARMACY
dc.description.doi10.1016/j.ymgme.2009.09.002
dc.description.sourcetitleMolecular Genetics and Metabolism
dc.description.volume99
dc.description.issue1
dc.description.page4-9
dc.description.codenMGMEF
dc.identifier.isiut000273758000002
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