ABSTRACT
This chapter considers species which are potential antimetabolites structurally related to phosphoenolpyruvate. It discusses the fundamental structural class of compounds that would be anticipated to be of utility as antimetabolites of pyrophosphatases are those related to methylenediphosphonic acid. The identification of an antimetabolite, some agent which inhibits or perturbs a given metabolic reaction, is a relatively simple, virtually trivial matter. The profound difficulty arises in the development of antimetabolites which will perform in a specific manner and be capable of being delivered intact to a specific reaction domain. For the design of specific antimetabolites based on the "phosphonic-acid-for-phosphate" concept, several "architectural" aspects must be given detailed consideration. The first of these is correspondence of steric factors between the natural phosphate and the postulated phosphonic acid antimetabolite. The phosphonic acids related to phosphatidic acid bearing normal carboxylate ester linkages have also been reported. Several systems have been reported bearing the C–P linkage in the backbone of the lipid.
