Credit: Courtesy of Alan Hawk / Historical Collections National Museum of Health and Medicine As biochemists during the 1970s delved into the protein chemistry of cell signaling, cycling, and adhesion, they ran into two major obstacles: getting enough purified material for some proteins, and the low molecular weights of others. Interferon, for example, was so difficult to purify that it" /> Credit: Courtesy of Alan Hawk / Historical Collections National Museum of Health and Medicine As biochemists during the 1970s delved into the protein chemistry of cell signaling, cycling, and adhesion, they ran into two major obstacles: getting enough purified material for some proteins, and the low molecular weights of others. Interferon, for example, was so difficult to purify that it" />
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The Dreyer Peptide and Protein Sequencer

Credit: Courtesy of Alan Hawk / Historical Collections National Museum of Health and Medicine" /> Credit: Courtesy of Alan Hawk / Historical Collections National Museum of Health and Medicine As biochemists during the 1970s delved into the protein chemistry of cell signaling, cycling, and adhesion, they ran into two major obstacles: getting enough purified material for some proteins, and the low molecular weights of others. Interferon, for example, was so difficult to purify that it

By | July 1, 2007

<figcaption> Credit: Courtesy of Alan Hawk / Historical Collections National Museum of Health and Medicine</figcaption>
Credit: Courtesy of Alan Hawk / Historical Collections National Museum of Health and Medicine

As biochemists during the 1970s delved into the protein chemistry of cell signaling, cycling, and adhesion, they ran into two major obstacles: getting enough purified material for some proteins, and the low molecular weights of others. Interferon, for example, was so difficult to purify that it took more than two decades before its structural characterization. And tiny proteins like angiotensin II (8 amino acids) and the antidiuretic hormone vasopressin (9 amino acids) produced hard-to-interpret protein signatures.

Biochemists were constantly pushing the limits of technology to couple, cleave, extract, and sequence peptides with better sensitivity. Pehr Edman, in 1950, developed a chemical degradation process for amino acid sequencing and built the first automated "sequenator" for that task in 1967. Richard Laursen, at Boston University, improved on Edman's concept in 1971 by immobilizing the study sample on a resin support. This made it possible to investigate smaller peptides, but liquid solvents in the process tended to wash out the sample, making scarce and low-molecular weight peptides difficult to capture.

Then, in 1977, Caltech biochemist William J. Dreyer developed the sequencer seen here.1 It featured a glass-cartridge reaction chamber with a macroporous support to immobilize peptides. Liquid and gas agents such as phenylisothiocyanate and trimethylamine gas are flowed through the chamber to bind the terminal residue on the peptide chain. Then, after washing, a strong anhydrous acid such as trifluoroacetic acid in vapor form cleaves the residue, which can be extracted with a solvent such as benzene. Drying stages using an inert gas (nitrogen) helped prevent washing out the sample, and the instrument was so sensitive, it could practically count individual ions.

Subsequently, Dreyer's former collaborators, Leroy Hood and Michael Hunkapiller, patented refinements to the highly sensitive instrument and used it to launch a product for Applied Biosystems. The move reportedly resulted in disputes over royalties and friction between the scientists.2

Dreyer's sequencer is now in the National Museum of Health and Medicine, part of the Armed Forces Institute of Pathology, in Washington, DC.

References

1. W.J. Dreyer, "Peptide or protein sequencing method and apparatus," US patent No. 4,065,412, issued Dec. 27, 1977. 2. Interview with William J. Dreyer, Oral History Project, California Institute of Technology Archives, 2005. http://oralhistories.library.caltech.edu/108/01/OH_Dreyer_W.pdf
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