My contributions to science from combination of bench experiments and quantum biology.

A. From stomach strip to quantum biology.

1. John R. Vane received Nobel medicine prize for the work on stomach strip (John R. Vane, Brit. J. Pharmacol. The Relative Activities of some Tryptamine Analogues on the Isolated Rat Stomach Strip Preparation) and related topics. But nobody could explain the results. Upon his request, I offered explanation of reason why such diverse activity related substituents varies and upon the recommendation of John Vane, I was invited to publish them in Nature (Kang, S. and Green, J.P.: Resonance constants and the activities of indolealkylamines on the stomach muscle. Nature 222: 794-795, 1969). I calculated the resonance constants using quantum mechanical electron densities calculation, which again correlated the Hammett constants, an empirical data, thereby establishing quantum chemical nature of stomach strip biology, namely a solid quantum biology for the first time.

 2. To strengthen my arguments, I measure carbon C-13 NMR of these compounds, and found an excellent correlation between biological data and C-13 electron densities (Kang, S., Ernst, L., Weinstein, H., and Osman, R.: Carbon-13 NMR chemical shifts and calculated electronic structures of serotonin congeners: Relation to biological activity. Mol. Pharmacol. 16: 1031-1039, 1979; Ernst, L. and Kang, S.: Carbon-13 NMR spectroscopy of substituted indoles and tryptamines I. J. Chem. Res. (S) 1981: 259, 1981; Ernst, L. and Kang, S.: Carbon-13 NMR spectroscopy of substituted indoles and tryptamines II. J. Chem. Res. (M) 1981: 3019-3038, 1981). It explains and predicts electronic shielding effects of nuclei.

 3. These unfailing electron density calculation led to understanding numerous characteristics of almost all biological molecules, small or macromolecules, thereby reducing or eliminating unnecessary experiments. It is a great triumph of human knowledge. It is my contribution.

 B. SSRI Structural Motif.

 4. Combined with electronic density variation, a certain structural motif or pharmacophore plays a fundamental role. Identification of these structural motifs is critical in understanding biological mechanism and drug design and development. I identified this structural motif for a series of indole alkylamines or pharmacophore, which leads a new series of SSRI-type antidepressant drugs such as Prozac, Zoloft, Citalopram, etc (Kang, S. and Green, J.P.: Steric and electronic relationships among some hallucinogenic compounds. Proc. Natl. Acad. Sci. USA. 67: 62-67, 1970).

The publication opened up a new world of antidepressant world. Further refinements are needed.

Pharmaceutical companies are not the first SSRI-type pharmacology development. They are based upon my PNAS publication, which also correctly predicted psycho-activity of tetralins congeners.

C. Other publications.

 5. There are numerous publications supporting the above two accomplishments and of unrelated topics, such as histamines, theoretical quantification of entropy, drug design of other area of disease, steroid inhibition of leucocyte activity (Muhlfelder, T., Niemetz, J., and Kang, S.: Glucocorticoids inhibit the generation of leucocyte procoagulant (tissue factor) activity. Blood 60(5): 1169-1172, 1982, isolation of tissue factor (Kang, S. and Niemetz, J.: Purification of human brain tissue factor. Thrombosis and Haemostasis, 59(3): 400-403, 1988), cholinergic receptor identification from fluorescence (Kang, S. and Maelicke, A.: Fluorescein isothiocyanate labeled alpha-cobra toxin: Biochemical characterization and interaction with acetylcholine receptor from electrophorus electricus. J. Biol. Chem. 255: 7326-7332, 1980), etc.

 

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