3180
Biochemistry 1980, 19, 3 180-3 186
Conformationally Restricted Creatine Analogues and Substrate Specificity of Rabbit Muscle Creatine Kinase? Robert F. Dietrich,$ Robert B. Miller, George L. Kenyon,* Thomas S. Leyh, and George H. Reed
ABSTRACT:
Several conformationally restricted analogues of creatine have been both synthesized and examined as potential substrates or inhibitors of rabbit muscle creatine kinase (EC 2.7.3.2). When a n asymmetric center was included in a creatine analogue in the position CY to the carboxyl group, the enzyme had a pronounced preference for the R enantiomer. Thus, whereas (R)-N-amidinoazetidine-2-carboxylic acid (7) has been shown to be a good substrate ( K , = 72 mM, K , = 39 mM, and V,,, = 29% relative to that of creatine) for creatine kinase, the corresponding S enantiomer 6 showed only barely detectable reactivity ( Vmax(rel). University of Pennsylvania School of Medicine. Philadelphia. Pennj! Ivdnia 19101 (T.S.L. and G.H.R.). Rereiced Drzeniber /?. 19'9. This work U P S supported b! U S . Public Health Service Relearch Grant5 .A\l I7323 (G.L.K.) and A31 17517 ( G H.R.). Thi, projea \\as ~ 1 x i3u p ported by the Divisisn of Research Resources. hational Institutsi of Health Grant R R 00892-01.-21 to the UCSF Magnetic Resonance Liborator). A preliminar! report of this work \\as presented a t the 63th Annual \leetin@ of the American Society of Biological Chemisti. ;\IIdnta, GA, June 1-8, 1978 (Dielrich 8: Ken!on. 197x). *Address corrcspondence to this author at the Department of Pharmaceutical Chemistr!. L'nivcr,it! of California Recipient of d Research Czreer Development Xuard, :\51 00014, from the Kational In,titute Arthritis, 3letabolism and Digr.sti\e Disea,es. 1975- 1980. 'Sational Institutes of Health Predoctoral Trdince. 19-6 -19'9 (Training Grant G31 00728 td the Department af Pharm.i;eutical Chemistr! ). Prcscnt address Department df Cheni:,tr!. Pccns!ltaniz State Lnitersit!. L'nivcrsit! Pirk. P:\ IhhO2
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