PCOL2605 Lecture Notes - Lecture 4: Circular Dichroism, Growth Hormone, Deamidation
23 Oct 2018
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To achieve them, you could optimise: for(cid:373)ulatio(cid:374, ad(cid:373)i(cid:374)istratio(cid:374) route, medical device. Indications: growth hormone deficiency in paediatric patients (also in adult patients) Molecular weight ~22,000 primary structure contains 191 amino acids, Hgh possess 9 asparagine and 13 glutamine residues which are susceptible to deamidation. The principal site of deamidation in alkaline ph is at asn-149. Deamidated hgh is indeed present in the pituitary. The deamidated form is as potent as the native hormone. The major oxidative reaction of hgh is at the methionine residue, producing the corresponding metsulfoxide. Met170 is buried inside the hgh molecular structure, hence not prone to react. Met-14 and met-125 can be oxidised but remain as potent, with no effect on the conformation as determined by circular dichroism and nmr spectroscopies. Surface denaturation followed by aggregation of the unfolded molecules. Divalent metal ions and surfactants stabilise the protein against aggregation. Methods to produce proteins in a dry form: freeze drying.
