|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
22
|
|
pubmed:dateCreated |
2011-6-1
|
|
pubmed:abstractText |
The ribosomal incorporation of nonnative amino acids into polypeptides in living cells provides the opportunity to endow therapeutic proteins with unique pharmacological properties. We report here the first clinical study of a biosynthetic protein produced using an expanded genetic code. Incorporation of p-acetylphenylalanine (pAcF) at distinct locations in human growth hormone (hGH) allowed site-specific conjugation with polyethylene glycol (PEG) to produce homogeneous hGH variants. A mono-PEGylated mutant hGH modified at residue 35 demonstrated favorable pharmacodynamic properties in GH-deficient rats. Clinical studies in GH-deficient adults demonstrated efficacy and safety comparable to native human growth hormone therapy but with increased potency and reduced injection frequency. This example illustrates the utility of nonnative amino acids to optimize protein therapeutics in an analogous fashion to the use of medicinal chemistry to optimize conventional natural products, low molecular weight drugs, and peptides.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
1091-6490
|
|
pubmed:author |
pubmed-author:AonMM,
pubmed-author:AxelrodDouglas WDW,
pubmed-author:BeckyG CGC,
pubmed-author:BuechlerYing JiYJ,
pubmed-author:BussellStuartS,
pubmed-author:CastiglioniPaolaP,
pubmed-author:ChuStephanieS,
pubmed-author:DanielTomT,
pubmed-author:DiMarchiRichard DRD,
pubmed-author:HoffmanAndrew RAR,
pubmed-author:JavahishviliTsotneT,
pubmed-author:KaphleSamiS,
pubmed-author:KimmelBruce EBE,
pubmed-author:KnudsenNickN,
pubmed-author:KraynovVadim SVS,
pubmed-author:LieuRickyR,
pubmed-author:LitzingerDavid CDC,
pubmed-author:MaioZhenweiZ,
pubmed-author:NormanThea CTC,
pubmed-author:OumaDD,
pubmed-author:PutnamAnna-Maria HaysAM,
pubmed-author:SchultzPeter GPG,
pubmed-author:SimBee-ChengBC,
pubmed-author:ViramontesGuillermoG
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
31
|
|
pubmed:volume |
108
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
9060-5
|
|
pubmed:meshHeading |
pubmed-meshheading:21576502-Animals,
pubmed-meshheading:21576502-Dose-Response Relationship, Drug,
pubmed-meshheading:21576502-Endocrinology,
pubmed-meshheading:21576502-Genetic Variation,
pubmed-meshheading:21576502-Human Growth Hormone,
pubmed-meshheading:21576502-Humans,
pubmed-meshheading:21576502-Male,
pubmed-meshheading:21576502-Mutation,
pubmed-meshheading:21576502-Peptides,
pubmed-meshheading:21576502-Phenylalanine,
pubmed-meshheading:21576502-Polyethylene Glycols,
pubmed-meshheading:21576502-Polymers,
pubmed-meshheading:21576502-Protein Engineering,
pubmed-meshheading:21576502-Rats,
pubmed-meshheading:21576502-Rats, Sprague-Dawley,
pubmed-meshheading:21576502-Ribosomes
|
|
pubmed:year |
2011
|
|
pubmed:articleTitle |
Optimized clinical performance of growth hormone with an expanded genetic code.
|
|
pubmed:affiliation |
Ambrx Incorporated, 10975 North Torrey Pines Road, La Jolla, CA 92037, USA. ho.cho@ambrx.com
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
