| pubmed-article:11562188 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11562188 | lifeskim:mentions | umls-concept:C0599840 | lld:lifeskim |
| pubmed-article:11562188 | lifeskim:mentions | umls-concept:C0033679 | lld:lifeskim |
| pubmed-article:11562188 | lifeskim:mentions | umls-concept:C0033666 | lld:lifeskim |
| pubmed-article:11562188 | lifeskim:mentions | umls-concept:C2603343 | lld:lifeskim |
| pubmed-article:11562188 | pubmed:issue | 5 | lld:pubmed |
| pubmed-article:11562188 | pubmed:dateCreated | 2001-9-19 | lld:pubmed |
| pubmed-article:11562188 | pubmed:abstractText | A guinea pig liver transglutaminase (G-TGase)-mediated procedure for the site-specific modification of chimeric proteins was recently reported. Here, an alternative method with advantages over the recent approach is described. This protocol utilizes a microbial transglutaminase (M-TGase) instead of the G-TGase as the catalyst. M-TGase, which has rather broad structural requirements as compared to the G-TGase, tends to catalyze an acyl transfer reaction between the gamma-carboxamide group of a intact protein-bound glutamine residue and various primary amines. To demonstrate the applicability of the M-TGase-catalyzed protein modification in a drug delivery system, we have utilized recombinant human interleukin 2 (rhIL-2) as the target protein and two synthetic alkylamine derivatives of poly(ethyleneglycol) (PEG12; MW 12 kDa) and galactose-terminated triantennary glycosides ((Gal)(3))) as the modifiers. For the M-TGase-catalyzed reaction with PEG12 and (Gal)(3), 1 mol of alkylamine was incorporated per mole of rhIL-2, respectively. Peptide mapping of (Gal)(3)-modified rhIL-2 ((Gal)(3)-rhIL-2) by liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS) suggested that the Gln74 residue in rhIL-2 was site specifically modified with (Gal)(3). The PEG12-rhIL-2 and (Gal)(3)-rhIL-2 conjugates retained full bioactivity relative to the unmodified rhIL-2. In pharmacokinetic studies, PEG12-rhIL-2 was eliminated more slowly from the circulation than rhIL-2, whereas (Gal)(3)-rhIL-2 accumulated in the liver via hepatic asialoglycoprotein receptor binding. The results of this study expand the applicability of the TGase-catalyzed methodology for the preparation of protein conjugates for clinical use. | lld:pubmed |
| pubmed-article:11562188 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11562188 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11562188 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:11562188 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11562188 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11562188 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11562188 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11562188 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11562188 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11562188 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11562188 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11562188 | pubmed:issn | 1043-1802 | lld:pubmed |
| pubmed-article:11562188 | pubmed:author | pubmed-author:SatoHH | lld:pubmed |
| pubmed-article:11562188 | pubmed:author | pubmed-author:HayashiEE | lld:pubmed |
| pubmed-article:11562188 | pubmed:author | pubmed-author:YamadaNN | lld:pubmed |
| pubmed-article:11562188 | pubmed:author | pubmed-author:TakaharaYY | lld:pubmed |
| pubmed-article:11562188 | pubmed:author | pubmed-author:YatagaiMM | lld:pubmed |
| pubmed-article:11562188 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:11562188 | pubmed:volume | 12 | lld:pubmed |
| pubmed-article:11562188 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11562188 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11562188 | pubmed:pagination | 701-10 | lld:pubmed |
| pubmed-article:11562188 | pubmed:dateRevised | 2004-11-17 | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:meshHeading | pubmed-meshheading:11562188... | lld:pubmed |
| pubmed-article:11562188 | pubmed:articleTitle | Further studies on the site-specific protein modification by microbial transglutaminase. | lld:pubmed |
| pubmed-article:11562188 | pubmed:affiliation | Ajinomoto Company Inc., Pharmaceutical Research Laboratories, 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki-shi, 210-8681, Japan. haruya_satou@ajinomoto.com | lld:pubmed |
| pubmed-article:11562188 | pubmed:publicationType | Journal Article | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:11562188 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:11562188 | lld:pubmed |
