Studies on Insulin

The Labile Amide in Insulin: Preparation of Desalanine-Desamido-Insulin*

“…The aliquots from the asparagine incubation were diluted several fold with the pH 2.2 buffer (Moore et al, 1958) and stored at -10°until submitted for amino acid analysis. Aliquots from the insulin incubation were treated differently depending upon whether the heat precipitate (Blatherwick et al, 1927;Du Vigneaud et al, 1928), designated fibrils by Waugh (1946), had formed. When fibrils were absent the aliquots were adjusted to pH 7.4 and submitted to the conditions for digestion by carboxypeptidase.…”

Specific Group Reagents for Proteins.

“…Where analytical data were not obtained, the results have not been included in table 2. The following references include a partial list (24,35,38,43,60,275,326).…”

The Chemical Synthesis of Insulin: An Enduring Challenge

“…However, there was early recognition that the hormone possesses physicochemical properties that posed major challenges to not only its regular handling but also its planned successful chemical preparation. In the late 1920s, it was observed that heating insulin in acidic solutions yielded an inactive precipitate. − Subsequent electron microscopy studies in the 1940s and 1950s showed that insulin undergoes a highly structured aggregation process known as fibrillation. − Head-to-tail insulin fibrillation can also occur via exposure of hydrophobic residues caused by a partially unfolded B-chain C-terminal segment . Furthermore, the A-chain is particularly susceptible to fibrillation.…”