7147. Pepstatin

Nomenclature

CAS number: 26305-03-3
N-(3-methyl-1-oxobutyl)-l-valyl-l-valyl-(3S,4S)-4-amino-3-hydroxy-6-methylheptanoyl-N-[(1S)-1-[(1S)-2-carboxy-1-hydroxyethyl]-3-methylbutyl]-l-alaninamide; Pepstatin A; N-isovaleryl-l-valyl-l-valyl-3-hydroxy-6-methyl-γ-aminoheptanoyl-l-alanyl-3-hydroxy-6-methyl-γ-aminoheptanoic acid.
C34H63N5O9; mol wt 685.89.
C 59.54%, H 9.26%, N 10.21%, O 20.99%.

Description and references

A pentapeptide pepsin inhibitor, isolated from cultured broths of Streptomyces testaceus Hamada et Okami and Streptomyces argenteolus var. toyonakensis: H. Umezawa et al., J. Antibiot. 23, 259 (1970). Prepn: H. Umezawa et al., DE 2028403 (1971 to Microbiochemical Res. Found.), C.A. 74, 75201c (1971). Structure: H. Morishima et al., J. Antibiot. 23, 263 (1970). Synthesis: H. Morishima et al., ibid. 25, 551 (1972). Biological properties: T. Aoyagi et al., ibid. 24, 687 (1971). N-n-Caproyl and N-iso-caproyl derivatives, pepstatin B and pepstatin C, also isolated from pepstatin-producing Streptomyces, as minor components of crude preparations: T. Miyano et al., ibid. 25, 489 (1972). Mechanism of pepsin inhibition: S. Kunimoto et al., ibid. 251; 27, 413 (1974); J. Marciniszyn et al., Adv. Exp. Med. Biol. 95, 199 (1977); D. H. Rich, E. T. O. Sun, Biochem. Pharmacol. 29, 2205 (1980); of other acid protease inhibition: D. H. Rich et al., Biochemistry 24, 3165 (1985). Tissue distribution in rats: D. A. W. Grant et al., Biochem. Pharmacol. 31, 2302 (1982). Effect on gastric ulcers in man: O. Bonnevie et al., Gut 20, 624 (1979); L. B. Svendsen et al., Scand. J. Gastroenterol. 14, 929 (1979).

Chemical structure

Properties

Colorless needles, mp 228-229° (dec). [α]D27 -90.3° (c = 0.288 in methanol). Sol in methanol, ethanol, acetic acid DMSO. Practically insol in benzene, chloroform, ether, and water. LD50 in mice, rats, rabbits, dogs (mg/kg): 1090, 875, 820, 450 i.p.; all >2000 orally (Umezawa, 1970).