Proteins, hormones study stability

It is well known that disulfane-containing compounds, such as proteins, hormones, Upoic acid, enzymes, and other products, occur naturally and many studies on their biochemical role have been published. Protein folding influenced by -S-S bridges of cystine has been studied intensively, and it is generally accepted now that introducing disulfane bonds into proteins thermally stabilizes the folded state. 

In many cases the most important aspect of structural studies is that knowledge of the structure of a protein leads to improved understanding of its function. For instance, if a protein has to be administered for lifetime or long-firm TAnjswmnii therapy (c.g, insulin, growth hormone, factor IX), it is import tant to know all about its stmcture-function-stability relationships. A longer turnover time or a higher specific activity, for example, allows for a smaller dose to... 

Storage stability has generally been the more serious stability issue faced with therapeutic proteins. Storage stability can be extremely formulation-specific [15,30,32,33], and even with a knowledge of the major degradation pathways in solution, selection of the optimum formulation for a solid is far from obvious. We illustrate the sensitivity of stability to formulation details with studies of an important protein product, human growth hormone. 

Circular dichroism (CD) has played an important role in our studies on the modification of enzymes and hormones with Co(III). The objective of these studies has been to incorporate selectively substitution inert metal ions at specifically modified sites in proteins as probes of biological function. Significant information concerning the catalytic mechanism of carboxypeptidase A (CPA) (1) has been obtained from a site specific modification of tyrosine 248 with Co(III) (2). The method developed for CPA has been extended to other enzymes and hormones in order to devg op an improved method for incorporating stable radioisotopes t Co) into proteins. The substitution-inertness of Co(III) provides the necessary stability in these derivatives (3). 

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