[1] His career was highlighted by synthesis of a prototype birth control pill, isolation and structural characterization of biotin (vitamin H), determination of the lysine specificity of the pancreatic protease trypsin (an attribute that made it the enzyme of first choice in protein sequence determinations), the first chemical synthesis of a fully biologically-active portion of the peptide hormone (adrenocorticotopic hormone - ACTH),[3] and structure-function studies on ribonuclease (RNase).
Hofmann was born in Germany but when his father died, his mother returned with her one-year-old son to her family home in Switzerland.
Switzerland, ringed by hostile forces, advised Hofmann, an officer in the Swiss militia, not to return for the course of the war.
In a few short years, the Dean of the School of Medicine, himself a professor of Biochemistry, invited Hofmann to become Chairman of the Department.
The burgeoning field of peptide chemistry became his scientific focus and, in his own words, he fell in love with a molecule that was known to stimulate the adrenal cortex to produce the very steroids that had so fascinated him in Reichstein's laboratory.
As a PhD student in the laboratories of future Nobel Laureates, Leopold Ruzicka and Tadeus Reichstein in Zürich, Hofmann synthesized a number of compounds related to terpenes, the hypothetical building block of steroids.
[5] Subsequently, with Vincent du Vigneaud, he used the newly developed technique of chromatography that he had learned while a student in Zürich, to isolate and then crystallize biotin.
[17] In the course of the peptide synthetic work on ACTH, a novel chain cleavage was observed at an acyl-proline linkage while removing protecting groups using metallic sodium in liquid ammonia.
[24][25] Once it was established that peptide hormone receptors resided on the plasma membrane of cells, direct studies of the activity of ACTH derivatives that had so long eluded researchers finally became a reality.
Hofmann and his colleagues isolated plasma membranes from beef adrenals[26] and were able to conduct structure-activity studies with synthetic analogs of ACTH.