Abstract: Novel inhibitors of polyamine transport having inhibition constants two orders of magnitude lower than those of known compounds are disclosed. These polyamine analogues are useful pharmaceutical agents for treating diseases where it is desired to inhibit polyamine transport or other polyamine binding proteins, for example cancer and post-angioplasty injury. Novel chemical synthetic methods to obtain polyamine analogues are disclosed, including the production of a combinational polyamine library. These approaches yield analogues with desirable activities both for diagnostic and research assays and therapy. The assays of the invention are useful for high throughput screening of targets in the discovery of drugs that interact with the polyamine system.

Abstract: A new paradigm of disease centers around the metabolic pathways of S-adenosyl-L-methionine (SAM), the intermediates of these pathways and other metabolic pathways influenced by the SAM pathways. Methods are provided to analyze and modulate SAM pathways associated with a disease or condition. Such methods permit identification and utilization of diagnostic and therapeutic protocols and agents for such disease states and conditions.

Abstract: Disclosed are novel methods, combinations of agents and kits for use in killing, or inhibiting the growth of, microorganisms. Enhanced antimicrobial action is provided by using a methylation inhibitor, as exemplified by using an agent that inhibits methylation or maturation of bacterial RNA in combination with, e.g., a macrolide lincosamide streptogramin B (MLS) antibiotic. The methods and compositions described may be employed to reduce the resistance of susceptible microorganisms to antimicrobial agents and thus to treat animals or patients with infections.