Purification and characterization by fast-atom-bombardment mass spectrometry of the polymorphonuclear-leucocyte-elastase-generated A alpha (1-21) fragment of fibrinogen from human blood after incubation with calcium ionophore A23187.

The stimulation of human blood with a Ca2+ ionophore, A23187, leads to activation of polymorphonuclear leucocytes (PMN) with release of small amounts of catalyticaly active elastase, as demonstrated by the formation of a characteristic product, the N-terminal A alpha (1-21) peptide of the Aa subunit of fibrinogen. The identity of the peptide was initially established by radioimmunoassay (r.i.

The structure of heneicomycin.

The antibiotic heneicomycin (1), C44H62N2O11, was isolated from cultures of Streptomyces filipinensis as an amorphous yellow powder. Mass spectral and NMR analysis showed the compound to be a deoxy modification of aurodox (2), a member of the elfamycin antibiotic family. A marked change in mass spectral fragmentation compared to aurodox and 1H NMR couplings indicated the absence of the hydroxyl at position 30 of aurodox (position 3 of the tetrahydropyran).

The structure of efrotomycin.

The antibiotic efrotomycin (I), C59H88N2O20, was isolated from cultures of Nocardia lactamdurans as an amorphous yellow powder. Mass spectral and NMR analyses show that the compound is a glycoside of the known antibiotic aurodox (II), C44H62N2O12. Ozonolysis and hydrolysis of I produced the disaccharide V, 6-deoxy-4-O-(6-deoxy-2,4-di-O-methyl-alpha -L-mannopyranosyl)-3-O-methyl-beta-D-allopyranose.

A potent nonpeptide cholecystokinin antagonist selective for peripheral tissues isolated from Aspergillus alliaceus.

A new, competitive, nonpeptide cholecystokinin (CCK) antagonist, asperlicin, was isolated from the fungus Aspergillus alliaceus. The compound has 300 to 400 times the affinity for pancreatic, ileal, and gallbladder CCK receptors than proglumide, a standard agent of this class. Moreover, asperlicin is highly selective for peripheral CCK receptors relative to brain CCK and gastrin receptors.

Biosynthesis of the beta-lactam antibiotic, thienamycin, by Streptomyces cattleya.

Radioactive- and stable isotope-containing substrates were used to identify the biosynthetic precursors of the beta-lactam antibiotic, thienamycin, in Streptomyces cattleya. Acetate is utilized by the organism to form C(6) and C(7) of the beta-lactam ring. The two carbons of the hydroxyethyl group attached to C(6) are both derived from the methyl of methionine.

L-155,175: a new antiparasitic macrolide. Fermentation, isolation and structure.

A new antiparasitic macrolide, L-155,175, produced by a strain of Streptomyces hygroscopicus, has been isolated; its structure was determined by physico-chemical means. It is active against the tapeworm Hymenolepis diminuta in rats.

Specific membrane receptors for atrial natriuretic factor in renal and vascular tissues.

Membranes from rabbit aorta and from rabbit and rat kidney cortex possess high-affinity (Kd = 10(-10) M) specific binding sites for atrial natriuretic factor (ANF). Similar high-affinity sites are present in an established cell line from pig kidney, LLC-PK1. Results of fractionation studies indicate that the receptors are localized in the plasma membrane of these tissues.

Discovery, production and purification of the Na+, K+ activated ATPase inhibitor, L-681,110 from the fermentation broth of Streptomyces sp. MA-5038.

The maximum yield for the production of L-681,110 by Streptomyces sp. MA-5038 (ATCC 31587) was observed after 5 days' incubation at 28 degrees C and pH about 8.3.

Isolation and sequence determination of peptide components of atrial natriuretic factor.

The independent isolation and sequence determination in our laboratories of three closely related Atrial Natriuretic Factor peptides from rat atria confirm the sequences of ANF peptides reported by Seidah et al and synthesized by Nutt et al [Proc. Natl. Acad.

Ivermectin: a potent new antiparasitic agent.

Ivermectin is the 22,23-dihydro derivative of avermectin B1, a macrocyclic lactone produced by an actinomycete, Streptomyces avermitilis. It is active at extremely low dosage against a wide variety of nematode and arthropod parasites, apparently by virtue of its action on the mediation of neurotransmission by gamma-aminobutyric acid. It is now in commercial use in various countries for the treatment and control of parasites in cattle, horses, and sheep, and is expected to become available for use in swine and dogs.

13C NMR study of thiostrepton and thiopeptin components.

A detailed 13C NMR study of thiostrepton and two series of thiopeptin components is consistent with their proposed structures and allows many unequivocal assignments to be made.

Total structure of the highly modified peptide antibiotic components of thiopeptin.

On the basis of 1H and 13C NMR evidence, the structures of two series of the highly modified sulfur-containing peptide antibiotic thiopeptin were elucidated.

The solution conformation of the peptide antibiotic thiostrepton: a 1H NMR study.

The majority of the 84 protons in the 1H NMR spectrum of thiostrepton at 300 MHz were unambiguously assigned on the basis of double resonance experiments under different conditions of solvent, temperature and 2H-exchange by comparison with the known crystal structure determined by Anderson et al.1) Evidence is presented to suggest that the side chain, the nature of which remained undefined on X-ray analysis, is comprised of two dehydroalanine residues which supports the conclusions reached by Tori et al.2) on the basis of 13C NMR spectroscopy.

Neocarzinostatin chromophore: presence of a highly strained ether ring and its reaction with mercaptan and sodium borohydride.

Spectroscopic evidence suggests the presence of a highly strained ether ring (Fig. 1) (possibly an epoxide) in the C12-subunit of the previously determined partial structure 2a (Fig. 2) of the major neocarzinostatin chromophore (NCS-Chrom A) which completes assignment of all the oxygens in the molecule.

Epithienamycins. II. Isolation and structure assignment.

At least six distinct beta-lactam antibiotics of the epithienamycin family are produced by a strain of Streptomyces flavogriseus MB 4638. Each of the six can be isolated in substantially pure form by column chromatography using Dowex 1, Amberlite XAD-2 and Biogel packings. The structures were established by comparison of the ultraviolet, proton magnetic resonance and mass spectral characteristics with those of thienamycin and its derivatives.

Dihydromevinolin, a potent hypocholesterolemic metabolite produced by Aspergillus terreus.

A new, potent hypocholesterolemic agent is produced by cultures of Aspergillus terreus. The isolation of the compound and its characterization as 4a,5-dihydromevinolin containing a trans-fused octahydro-naphthalene system are described. Comparative data for dihydromevinolin and mevinolin in three biological assays are given: in vitro inhibition of HMG-CoA reductase, inhibition of sterol synthesis in cell cultures, and inhibition of cholesterol synthesis in vivo in rats.

Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent.

Mevinolin, a fungal metabolite, was isolated from cultures of Aspergillus terreus. The structure and absolute configuration of mevinolini and its open acid form, mevinolinic acid, were determined by a combination of physical techniques. Mevinolin was shown to be 1,2,6,7,8,8a-hexahydro-beta, delta-dihydroxy-2,6-dimethyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-hepatanoic acid delta-lactone.

Avermectins, new family of potent anthelmintic agents: isolation and chromatographic properties.

The avermectins, a family of new anthelmintic agents, were isolated from the mycelia of Streptomyces avermitilis. Four closely related major components and four homologous minor components were separated from the complex. Solvent extraction, solvent partition, and adsorption methods were used to isolate and purify the complex; novel partition chromatography systems using Sephadex LH-20 were used to separate the components.