A new alternation of semisynthetic, water-soluble pneumocandin analogs has been begin to be acutely almighty adjoin Pneumocystis carinii in an immunocompromised-rat model. These compounds are 5 to 10 times added almighty than the ancestor accustomed product, pneumocandin B0 (L-688,786) (R. E. Schwartz et al., J. Antibiot. 45:1853-1866, 1992), and > 100 times added almighty than cilofungin. One admixture in particular, L-733,560, had a 90% able dosage adjoin P. carinii cysts of 0.01 mg/kg of physique weight if delivered parenterally (subcutaneously, alert circadian for 4 days). The pneumocandins are accustomed lipopeptide articles of the echinocandin chic which arrest the amalgam of 1,3-beta-D-glucan in affected fungi. The abridgement of a agnate alleyway in beastly hosts makes this approach of activity an adorable one for alleviative systemic infections. Substitution by an aminoethyl ether at the hemiaminal and aridity and abridgement of the glutamine of pneumocandin B0 produced a semisynthetic admixture (L-733,560) with built-in baptize solubility, decidedly added potency, and a broader antifungal spectrum. To appraise the apparatus for the bigger antifungal efficacy, we bent that L-733,560 was a added almighty inhibitor of glucan synthase activity in vitro, did not affect the added membrane-bound enzymes tested, conferred susceptibility to lysis in the absence of osmotic support, and did not agitate currents in liposomal bilayers or 86Rb+ fluxes from liposomes. In Aspergillus breed L-733,560 aswell produced the aforementioned morphological alterations as pneumocandin B0. A stereoisomer of L-733,560 with poor antifungal activity was a anemic inhibitor of glucan synthase. All of these after-effects abutment the angle that the added antifungal activity of L-733,560 is accomplished by above inhibition of glucan amalgam and not by all-embracing film furnishings or a additional approach of action.