The research career of Richard B. Stein (1940-)

This report reviews the research and mentoring career of Richard B. Stein (1940-). In 1962, he completed a B.S. degree in physics at the Massachusetts Institute of Technology, USA, and thereafter an M.A. (1964), Ph.D. (1966), and postdoctoral training (1966-68) at the University of Oxford, UK. He subsequently assumed a faculty position at the University of Alberta (Canada), where he is currently an active researcher and mentor. To this point in 2004, Stein has trained and collaborated closely with over 160 scientists, largely neuroscientists and biomedical engineers, from 27 countries. He and his former trainees and collaborators have made important contributions on topics that span the cellular-to-behavioral spectrum of movement and rehabilitation-prosthetics neuroscience. His mentors, trainees, and collaborators include scientists whose countries of origin are: Australia, 2; Austria, 1; Belgium, 1; Bulgaria, 1; Canada, 64; China, 6; Denmark, 1; Germany, 1; Great Britain, 16; Hong Kong, 4; India, 5; Iraq, 2; Italy, 2; Japan, 10; Kenya, 1; New Zealand, 4; Pakistan, 1; Palestine, 1; Poland, 1; Romania, 1; South Africa, 1; Sri Lanka, 1; The Netherlands, 1; Turkey, 1; Uruguay, 1; USA, 21; and Yugoslavia, 6. In all instances, Stein's research collaborations and mentoring have advanced the careers of his trainees and junior collaborators, a well-deserved and important compliment to a stellar movement neuroscientist.     

(2R,3S)-(+)- and (2S,3R)-(-)-Halofuginone lactate: synthesis, absolute configuration, and activity against Cryptosporidium parvum

The trans-enantiomers of the commercially important anti-protozoal compound Halofuginone have been prepared and characterized, and the absolute configuration was assigned by X-ray crystallography. The activity of both enantiomers against Cryptosporidium parvum was determined in vitro and related to acute toxicity in vivo. It was shown that both the activity and the toxicity are properties of the (2R,3S)-enantiomer. We conclude that with respect to broadening the therapeutic window there is no advantage in application of one enantiomer over the application of the racemic mixture in the treatment of C. parvum infections.     

Primary deuterium isotope effects for the 3-methylaspartase-catalyzed deamination of (2S)-aspartic acid, (2S,3S)-3-methylaspartic acid, and (2S,3S)-3-ethylaspartic acid

3-Methylaspartate ammonia-lyase catalyzes the deamination of (2S)-aspartic acid 137 times more slowly than the deamination of (2S,3S)-3-methylaspartic acid but catalyzes the amination of fumaric acid 1.8 times faster than the amination of mesaconic acid [Botting, N.P., Akhtar, M., Cohen, M. A., & Gani, D. (1988) Biochemistry (preceding paper in this issue)]. In order to understand the mechanistic basis for these observations, the deamination reaction was examined kinetically with (2S)-aspartic acid, (2S,3S)-3-methylaspartic acid, (2S,3S)-3-ethylaspartic acid, and the corresponding C-3-deuteriated isotopomers. Comparison of the double-reciprocal plots of the initial reaction velocities for each of the three pairs of substrates revealed that the magnitude of the primary isotope effect on both Vmax and V/K varied with the substituent at C-3 of the substrate. 3-Methylaspartic acid showed the largest isotope effect (1.7 on Vmax and V/K), 3-ethylaspartic acid showed a smaller isotope effect (1.2 on Vmax and V/K), and aspartic acid showed no primary isotope effect at all. These results, which are inconsistent with earlier reports that there is no primary isotope effect for 3-methylaspartic acid [Bright, H. J. (1964) J. Biol. Chem. 239, 2307], suggest that for both 3-methylaspartic acid and 3-ethylaspartic acid elimination occurs via a predominantly concerted mechanism whereas for aspartic acid an E1cb mechanism prevails.(ABSTRACT TRUNCATED AT 250 WORDS)     

Practical access to the proline analogs (S,S,S)- and (R,R,R)-2-methyloctahydroindole-2-carboxylic acids by HPLC enantioseparation

An efficient methodology for the preparation of the α‐tetrasubstituted proline analog (S,S,S)‐2‐methyloctahydroindole‐2‐carboxylic acid, (S,S,S)‐(αMe)Oic, and its enantiomer, (R,R,R)‐(αMe)Oic, has been developed. Starting from easily available substrates and through simple transformations, a racemic precursor has been synthesized in excellent yield and further subjected to HPLC resolution using a cellulose‐derived chiral stationary phase. Specifically, a semipreparative (250 mm × 20 mm ID) Chiralpak® IC column has allowed the efficient resolution of more than 4 g of racemate using a mixture of n‐hexane/tert‐butyl methyl ether/2‐propanol as the eluent. Multigram quantities of the target amino acids have been isolated in enantiomerically pure form and suitably protected for incorporation into peptides. Chirality, 2011. © 2011 Wiley‐Liss, Inc.