Towards A Synthesis Of Potential Transition State Analog Inhibitors Of Orotate Phosphoribosyltransferase PDF Download

The transItIOn-state theory has been, from the point of its inception, the most influential principle in the development of our knowledge of reaction mechanisms in solution. It is natural that as the field of biochemical dynamics has achieved new levels of refinement its students have increasingly adopted the concepts and methods of transition-state theory. Indeed, every dynamical problem of biochemistry finds its most elegant and economical statement in the terms of this theory. Enzyme catalytic power, for example, derives from the interaction of enzyme and substrate structures in the transition state, so that an understanding of this power must grow from a knowledge of these structures and interactions. Similarly, transition-state interactions, and the way in which they change as protein structure is altered, constitute the pivotal feature upon which molecular evolution must turn. The complete, coupled dynamical system of the organism, incorporating the transport of matter and energy as well as local chemical processes, will eventually have to yield to a description of its component transition-state structures and their energetic response characteristics, even if the form of the description goes beyond present-day transition-state theory. Finally, the importance of biochemical effectors in medicine and agriculture carries the subject into the world of practical affairs, in the use of transition-state information for the construction of ultra potent biological agents.