isolated from Streptomyces lincolnensis. Lincomycin (9.87) is the prototype compound
in this class. It consists of a pyrrolidine moiety (trans-L-n-propylhygric acid) and a
sugar moiety (α-thiolincosamide) connected by an amide bond. Replacement of the
7(R)-hydroxy group of lincomycin with a chlorine and subsequent inversion of configu-
ration leads to 7(S)-chloro-7-deoxylincomycin (9.88, clindamycin), which has also
been used clinically. Lincomycins are primarily active against Gram-positive bacteria,
particularly the cocci. The use of clindamycin has been associated with gastrointestinal
toxicity, including a very serious form of diarrhea called pseuodomembranous colitis.
9.4.4 Antibacterials Targeting Bacterial Nucleic AcidsAnother logical means of confronting the diseases of bacterial infection is to prevent the
bacteria from reproducing. This may be readily achieved by targeting the bacterial
nucleic acids.
9.4.4.1 Antibacterials Targeting Dihydrofolate Reductase: Sulfas
Dihydrofolate reductase (E.C. 1.5.1.3) is a relatively small monomeric protein (MW =
18,000–36,000) containing no disulfide bonds. It is present in all cells in different
isozyme forms that depend on the organism. The best studied form contains 159 amino
acids, with 30% of them in an eight-stranded pleated sheet. The binding site is a 1.5 nm
EXOGENOUS PATHOGENS AND TOXINS 577