Unnatural amino acids combine with HGH to make for better therapy

[n2doc]

By Diana Gitig | Published about 16 hours ago

The universal genetic code allows for 20 amino acids to be used in proteins. They can be smaller, bigger, acidic, basic, polar, nonpolar, linear, or with rings—but there are only 20. Of course there are plenty of other amino acids that can be synthesized, but DNA cannot instruct cells to put them into proteins.

Or at least it couldn’t until 2001, when researchers at The Scripps Institute in La Jolla published a paper, entitled "Expanding the genetic code of Escherishia coli," in Science. They described the creation of a unique tRNA/aminoacyl-tRNA synthetase enzyme pair that incorporated a synthetic amino acid into proteins in bacteria. Similar feats have since been accomplished in eukaryotic and mammalian cells, and a new report in PNAS uses the technique to make a modified protein with clinical relevance: human growth hormone (hGH).

Humans who don’t make enough of their own growth hormone can be treated with recombinant hGH, but because it is so small, it is cleared very rapidly by the kidneys. Thus, successful treatment consists of daily injections.

A common way to increase the circulating half-life of peptide drugs in the body, which enables lower doses and/or less-frequent administration, is to link them to polyethylene glycol (PEG). PEG consists of a repeating chain of ethylene oxide moieties. Once they are linked to a peptide, each ethylene glycol subunit becomes tightly associated with two or three water molecules. This has the dual function of rendering the peptide more soluble in water and making it larger. Since the kidneys filter substances by size, the addition of PEG’s molecular weight cuts down on the speed with which they pass through the kidneys. PEG’s globular structure also acts as a shield to protect the peptide from proteolytic degradation, and can reduce the immunogenicity of foreign peptides by reducing uptake by dendritic cells.

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http://arstechnica.com/science/news/2011/05/unnatural-amino-acids-combine-with-hgh-to-make-for-better-therapy.ars