Two minor components of tuberactinomycin have been isolated from cultures of Streptomyces griseoverticillatus var. tuberacticus1) and named tuberactinomycin B and tuberactinomycin O. Tuberactinomycin O is a new member of the tuberactinomycin family with biological activity similar to that of tuberactinomycin N. Tuberactinomycin B, on the other hand, has properties similar to viomycin and is considered to be identical with it. The characterization and properties of these two antibiotics are reported in this paper.
A new crystalline antibiotic named vermiculine has been isolated from the fermentation broth of Penicillium vermiculatum DANGEARD. Vermiculine is a neutral colorless substance melting at 175-177°C with decomposition, containing only C, H and O. (λmax. 222mμ in methanol). The antibiotic inhibits growth of Trypanosoma cruzi, Leishmania braziliensis and some Grampositive bacteria.
Streptomycin, kanamycin, gentamicin, and kasugamycin were observed to inhibit f2 phage RNA-directed protein synthesis in an Escherichia coli system. When the reaction mixture was allowed to translate viral RNA for 5 minutes before addition of antibiotics, the synthesis was completely blocked by streptomycin or thiopeptin; but significant synthesis continued in the presence of kasugamycin, kanamycin and gentamicin. The results suggested that kasugamycin, kanamycin and gentamicin may inhibit initiation, and streptomycin may interfere with both chain initiation and elongation. Thiopeptin may affect chain elongation. The binding of fMet-tRNA to 70S ribosomes in the presence of f2 RNA was inhibited by streptomycin, kanamycin, gentamicin, and kasugamycin. The release of fMet-tRNA from the initiation complex was significantly induced by streptomycin, kanamycin, and gentamicin; but not by kasugamycin. The results indicated that the inhibition by kasugamycin of 30S initiation complex formation may result in the apparent inhibition of 70S initiation complex formation. And the apparent inhibition by streptomycin, kanamycin, and gentamicin of 70S initiation complex formation may be caused by breakdown of the complex and inhibition of ribosomal dissociation. The effects of streptomycin, kanamycin, and gentamicin were more significant with the initiation complex formed on washed 70S ribosomes than with the complex formed on unwashed 70S ribosomes. The ribosomal proteins washed out in 1 M NH4Cl protected the target sites from the antibiotic actions. The T factor- and messenger-dependent binding of Ala-tRNA to the ribosomes was significantly affected by streptomycin, but not by kanamycin, gentamicin, and kasugamycin.
Carbenicillin is capable of inactivating gentamicin in vitro. This effect is time, temperature and medium dependent. In vitro antibacterial tests demonstrate greater than additive activity in some instances and inactivation in others, particularly after prolonged incubation. Inactivation was not observed in vivo in mouse protection tests. Additive or more than additive combined activity in mouse protection tests occurred only infrequently. Intravenous administration of carbenicillin had no effect on gentamicin serum levels (given i.m.) in dogs although it did result in reduced recovery of gentamicin in the urine. This may have occurred after the urine had left the bladder. It is important that serum samples containing both gentamicin and carbenicillin be assayed shortly after drawing since inactivation can occur in these samples which then might be falsely interpreted as in vivo inactivation.
Moenomycin contains phosphorus which is present in diester linkage. During hydrolysis a phosphoric monoester, P4, is obtained which is converted into the polyhydroxycarboxylic acid D4 by enzymatic dephosphorylation. The structure of P4 has been identified as D-phosphoglycerate. The position of the phosphate group is still not clear. D4 is identical with D-glyceric acid.
Culture Streptomyces coelicolor MÜLLER NRRL 3532 deactivates clindamycin. The inactive compound identified as clindamycin-3-phosphate on treatment with dephosphorylating enzymes affords the active compound, clindamycin. In as much as the 2-phosphate ester of clindamycin is being clinically evaluated as an injectable form of clindamycin, it was of interest to compare its in vitro and in vivo characteristics with the 3-phosphate ester. Analysis of the kinetics of hydrolysis of the esters in three in vitro enzyme systems indicate marked differences, with the 3-ester being hydrolyzed much more slowly and much less extensively than the 2-ester. An in vivo study in rats revealed lower blood levels for the 3-phosphate when compared with the 2-- phosphate and may be related to the rates of hydrolysis. Metabolism studies indicate that the esters are metabolized in a similar manner to the parent clindamycin.
A dopamine β-hydroxylase inhibitor produced by Gloeophyllum striatum was isolated and found to be identical with oosponol. The inhibition is competitive with tyramine and noncompetitve with ascorbic acid. This inhibitor showed a hypotensive effect.
Gatavalin, a new peptide antibiotic, was isolated from cells of Bacillus polymyxa var. colistinus KOYAMA. The antimicrobial spectrum of this antibiotic is characterized by activity against gram-positive bacteria, mycobacteria, yeasts and molds. This antibiotic was named gatavalin because it contains glutamic acid, aspartic acid, threonine, alanine and valine. The isolation, purification, physico-chemical and biological properties of gatavalin are described, and the relationship with other colistinus peptides, colistin and jolipeptin, is discussed.
The utility of acetyl mixed anhydride as a carboxylic acid blocking group during acylamido cleavage of cephalosporins and penicillins is illustrated. The formation of N-chloroacetyl cephalosporin C in the isolation of cephalosporin C is described.
Pepstatin, a specific inhibitor of acid proteases, binds tightly to pepsin. Although the binding is not of the covalent nature, the inhibition roughly follows the stoicheometrical mode. Pepstatin can be used to titrate pepsin. Formation of an equimolar pepsin-pepstatin complex can be shown by gel filtration. Diacetylpepstatin, which has weaker activity than pepstatin competitively inhibits pepsin with a dissociation constant of 7.3×1O-6M. Data of pepstatin binding of chemically modified pepsins suggested that pepstatin binds with the active site surrounded by two aspartic acid moieties.