Synthetic enzyme pioneer dies

Ralph F. Hirschmann, a medicinal chemist who was one of the first to synthesize an enzyme in the lab, died last week (June 20) at age 87 from renal disease complications. Image: University of Pennsylvania"He was extraordinarily forward thinking," said organic chemist linkurl:Jeff Winkler,;http://webdev.chem.upenn.edu/chem/research/faculty.php?id=39 Hirschmann's colleague at the University of Pennsylvania. "His work was really revolutionary in that he achieved things that at the time were imagin

Jef Akst

| 2 min read

Ralph F. Hirschmann, a medicinal chemist who was one of the first to synthesize an enzyme in the lab, died last week (June 20) at age 87 from renal disease complications.

Image: University of Pennsylvania

"He was extraordinarily forward thinking," said organic chemist linkurl:Jeff Winkler,;http://webdev.chem.upenn.edu/chem/research/faculty.php?id=39 Hirschmann's colleague at the University of Pennsylvania. "His work was really revolutionary in that he achieved things that at the time were imagined virtually inconceivable." After receiving his PhD in organic chemistry from the University of Wisconsin, Madison, in 1950, Hirschmann started his work for Merck Research Laboratories, which lasted for almost 40 years. During that time, he and his colleague Robert G. Denkewalter succeeded in constructing the first synthetic enzyme, a feat that had long stumped chemists and "a real landmark achievement in medicinal chemistry," Winkler said. Concurrently, R. Bruce Merrifield and Bernd Gutte of the Rockefeller University in New York also synthesized the same enzyme using another method, and both teams presented their results at a news conference at Rockefeller in 1969. Hirschmann and Denkewalter published their work in the Journal of the American Chemical Society; the five papers have been cumulatively cited more than 200 times, according to ISI. During his time with Merck, Hirschmann led many research programs that resulted in the development of new medicines widely used today. These include Lisinopril for the treatment of hypertension and congestive heart failure, Vasotec for lowering high blood pressure, and Proscar for treating prostate cancer. When Hirschmann retired from Merck, he joined the chemistry department at the University of Pennsylvania, where he collaborated with U Penn colleague linkurl:Amos B. Smith;http://webdev.chem.upenn.edu/chem/research/faculty.php?id=33 and linkurl:K.C. Nicolaou;http://www.scripps.edu/research/faculty.php?rec_id=499 of the Scripps Research Institute to found the field of peptidomimetics -- the creation of nonpeptide molecules designed to mimic proteins. "He started really a new area," said Hirschmann's U Penn colleague linkurl:Madeleine Joullie.;http://www.chem.upenn.edu/chem/research/faculty.php?id=23 "When you have the whole peptide it's very hard to figure out what's going on. [With peptidomemtics], you can actually mimic some of the work of the peptides [to] single out special functions in molecules that are important to the way the peptide acts in the body." Throughout his career, Hirschmann has received many honors, including the National Medal of Science presented by President Bill Clinton in 2000, an induction into the ACS Medicinal Chemistry Hall of Fame in 2007, and inductions into both the American Academy of Arts & Sciences and the National Academy of Sciences. He published more than 150 papers and more than 100 patents. "His intellectual depth was really unparalleled," Winkler said. "He was a fine man, and we miss him very much."
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