Arginine-pyrimidine conjugates with therapeutic and prophylactic activity in lethal bacterial infections.

Arginine-pyrimidine conjugates represent a novel class of compounds that exhibits therapeutic and prophylactic activity in lethal infections by Gram-positive and Gram-negative bacteria without showing antibacterial activity in vitro.

A practical total synthesis of the microbial alkaline proteinase inhibitor (MAPI).

Diverse serine and cysteine proteases as well as alkaline proteinases and elastases play a crucial role in numerous biological processes. Natural peptide aldehydes such as the "microbial alkaline proteinase inhibitor" (MAPI, 1) are valuable tools to characterize novel enzymes and to study their function in nature. Within a drug discovery program we wanted to design and explore non-natural MAPI congeners with novel biological profiles.

Lost in transcription--inhibition of RNA polymerase.

Form and function: The natural product myxopyronin A provides the key to understanding the inhibition of bacterial RNA polymerase and should spark new ideas for the design of new antibiotics against tuberculosis and other infectious diseases.

Biological characterization of novel inhibitors of the gram-positive DNA polymerase IIIC enzyme.

Novel N-3-alkylated 6-anilinouracils have been identified as potent and selective inhibitors of bacterial DNA polymerase IIIC, the enzyme essential for the replication of chromosomal DNA in gram-positive bacteria. A nonradioactive assay measuring the enzymatic activity of the DNA polymerase IIIC in gram-positive bacteria has been assembled. The 6-anilinouracils described inhibited the polymerase IIIC enzyme at concentrations in the nanomolar range in this assay and displayed good in vitro activity (according to their MICs) against staphylococci, streptococci, and enterococci.