Abraham Patchornik: The Contemporary Relevance of His Work for Chemistry and Biology.

Abraham Patchornik was born in 1926 in Ness Ziona, a town in Palestine founded by his great-grandfather Reuben Lehrer in 1883. He started to study chemistry as an undergraduate at the Hebrew University. However, this was interrupted by the war, and he completed his studies in various locations in West Jerusalem. From 1952 to 1956 Patchornik completed his PhD at the (new) Weizmann Institute of Science with Ephraim Katchalski. After a postdoc at the NIH, he returned to the Weizmann in 1958, when he joined the Department of Biophysics. In 1972-1979, he became chairman of the new Department of Organic Chemistry at the Weizmann, and his own research was geared toward applying creative chemistry to solve biological problems. Patchornik passed away in his hometown of Ness Ziona in 2014. Patchornik was a conceptual leader in peptide and polymer chemistry. Given the importance of selective functional group protection for the construction of oligomeric molecules, he became interested in using "nonstandard", orthogonal chemistry for this purpose, i.e. photosensitive protecting groups (PPGs) in place of thermal reactions. It was R.B. Woodward who suggested this strategy to Patchornik in 1965, while Patchornik was on sabbatical leave at Harvard. However, it was not until Patchornik returned to the Weizmann that this idea of a versatile PPG to enable multistep synthesis was realized. Here, we provide an account of the early photosensitive protecting groups that Patchornik and co-workers developed, and the immense impact they have had on various fields. In particular, we survey the use of PPGs in live cell physiology (i.e., caged compounds), and the development of gene chips via light-directed solid-phase synthesis. Further, we highlight recent work applying new PPGs for "photochemical delivery" of drugs, otherwise termed photopharmacology. Finally, we discuss the relationship between caged compounds and how contemporary neuroscience uses genetically encoded chromophores to control cell function.