| pubmed-article:19706892 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19706892 | lifeskim:mentions | umls-concept:C0031327 | lld:lifeskim |
| pubmed-article:19706892 | lifeskim:mentions | umls-concept:C0033684 | lld:lifeskim |
| pubmed-article:19706892 | lifeskim:mentions | umls-concept:C0184511 | lld:lifeskim |
| pubmed-article:19706892 | lifeskim:mentions | umls-concept:C0018270 | lld:lifeskim |
| pubmed-article:19706892 | lifeskim:mentions | umls-concept:C0444498 | lld:lifeskim |
| pubmed-article:19706892 | lifeskim:mentions | umls-concept:C0301869 | lld:lifeskim |
| pubmed-article:19706892 | pubmed:issue | 36 | lld:pubmed |
| pubmed-article:19706892 | pubmed:dateCreated | 2009-10-6 | lld:pubmed |
| pubmed-article:19706892 | pubmed:abstractText | The challenge in the synthesis of protein-polymer conjugates for biological applications is to synthesize a stoichiometric (typically 1:1) conjugate of the protein with a monodisperse polymer, with good retention of protein activity, significantly improved pharmacokinetics and increased bioavailability, and hence improved in vivo efficacy. Here we demonstrate, using myoglobin as an example, a general route to grow a PEG-like polymer, poly(oligo(ethylene glycol) methyl ether methacrylate) [poly(OEGMA)], with low polydispersity and high yield, solely from the N-terminus of the protein by in situ atom transfer radical polymerization (ATRP) under aqueous conditions, to yield a site-specific (N-terminal) and stoichiometric conjugate (1:1). Notably, the myoglobin-poly(OEGMA) conjugate [hydrodynamic radius (R(h)): 13 nm] showed a 41-fold increase in its blood exposure compared to the protein (R(h): 1.7 nm) after IV administration to mice, thereby demonstrating that comb polymers that present short oligo(ethylene glycol) side chains are a class of PEG-like polymers that can significantly improve the pharmacological properties of proteins. We believe that this approach to the synthesis of N-terminal protein conjugates of poly(OEGMA) may be applicable to a large subset of protein and peptide drugs, and thereby provide a general methodology for improvement of their pharmacological profiles. | lld:pubmed |
| pubmed-article:19706892 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19706892 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19706892 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19706892 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19706892 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:19706892 | pubmed:issn | 1091-6490 | lld:pubmed |
| pubmed-article:19706892 | pubmed:author | pubmed-author:ZalutskyMicha... | lld:pubmed |
| pubmed-article:19706892 | pubmed:author | pubmed-author:TooneEric JEJ | lld:pubmed |
| pubmed-article:19706892 | pubmed:author | pubmed-author:ChilkotiAshut... | lld:pubmed |
| pubmed-article:19706892 | pubmed:author | pubmed-author:LiuWengeW | lld:pubmed |
| pubmed-article:19706892 | pubmed:author | pubmed-author:MackayJ... | lld:pubmed |
| pubmed-article:19706892 | pubmed:author | pubmed-author:GaoWeipingW | lld:pubmed |
| pubmed-article:19706892 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19706892 | pubmed:day | 8 | lld:pubmed |
| pubmed-article:19706892 | pubmed:volume | 106 | lld:pubmed |
| pubmed-article:19706892 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19706892 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19706892 | pubmed:pagination | 15231-6 | lld:pubmed |
| pubmed-article:19706892 | pubmed:dateRevised | 2011-5-13 | lld:pubmed |
| pubmed-article:19706892 | pubmed:meshHeading | pubmed-meshheading:19706892... | lld:pubmed |
| pubmed-article:19706892 | pubmed:meshHeading | pubmed-meshheading:19706892... | lld:pubmed |
| pubmed-article:19706892 | pubmed:meshHeading | pubmed-meshheading:19706892... | lld:pubmed |
| pubmed-article:19706892 | pubmed:meshHeading | pubmed-meshheading:19706892... | lld:pubmed |
| pubmed-article:19706892 | pubmed:meshHeading | pubmed-meshheading:19706892... | lld:pubmed |
| pubmed-article:19706892 | pubmed:meshHeading | pubmed-meshheading:19706892... | lld:pubmed |
| pubmed-article:19706892 | pubmed:meshHeading | pubmed-meshheading:19706892... | lld:pubmed |
| pubmed-article:19706892 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:19706892 | pubmed:articleTitle | In situ growth of a stoichiometric PEG-like conjugate at a protein's N-terminus with significantly improved pharmacokinetics. | lld:pubmed |
| pubmed-article:19706892 | pubmed:affiliation | Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708-0281, USA. | lld:pubmed |
| pubmed-article:19706892 | pubmed:publicationType | Journal Article | lld:pubmed |
