ABSTRACT
The angiotensin-I-converting enzyme (ACE) inhibitory activity of a tryptic digest of bovine beta-lactoglobulin (beta-lg) was investigated. Intact beta-lg essentially did not inhibit ACE while the tryptic digest gave an 84.3% inhibition of ACE. Peptide material eluting between 20 and 25% acetonitrile during C18 solid-phase extraction of the beta-lg tryptic digest inhibited ACE by 93.6%. This solid-phase extraction fraction was shown by mass spectroscopy to contain beta-lg f(142-148). This peptide had an ACE IC50 value of 42.6 micromol/l. The peptide was resistant to further digestion with pepsin and was hydrolysed to a very low extent with chymotrypsin. The contribution of specific amino acid residues within the peptide to ACE inhibitory activity and the potential application of this peptide as a nutraceutical is discussed.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/chemistry , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Lactoglobulins/chemistry , Lactoglobulins/pharmacology , Peptide Fragments/pharmacology , Peptidyl-Dipeptidase A/metabolism , Amino Acid Sequence , Animals , Cattle , Chromatography, High Pressure Liquid , Chymotrypsin , Kinetics , Pepsin A , Peptide Fragments/chemistry , Peptide Fragments/isolation & purification , Peptide Mapping , Rabbits , TrypsinABSTRACT
Novel angiotensin-I-converting enzyme (ACE) inhibitory activities were detected in synthetic peptides corresponding to sequences of beta-lactoglobulin and alpha-lactalbumin and which are known to possess opioid activity. Using hippuryl-histidyl-leucine as substrate, the tetrapeptides beta-lactorphin (Tyr-Leu-Leu-Phe), alpha-lactorphin (Tyr-Gly-Leu-Phe) and beta-lactotensin (His-Ile-Arg-Leu) were shown to have IC50 values of 171.8, 733.3 and 1153.2 microM, respectively. Related dipeptides also inhibited ACE, with Tyr-Leu being the most potent, having an IC50 value of 122.1 microM.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Lactalbumin/chemistry , Lactoglobulins/chemistry , Oligopeptides/pharmacology , Angiotensin-Converting Enzyme Inhibitors/chemical synthesis , Angiotensin-Converting Enzyme Inhibitors/chemistry , Caseins/chemistry , Dipeptides/pharmacology , Oligopeptides/chemical synthesis , Oligopeptides/chemistryABSTRACT
A novel series of carbocyclic compounds has been isolated from two related Micromonospora cultures. The C-19 and C-22 macquarimicins represent different end products on a similar biosynthetic scheme. 1-D and 2-D homonuclear and heteronuclear NMR experiments allowed assignment of the basic structures of the macquarimicins. An X-ray structure of macquarimicin B suggested the stereochemistry for the series which was not discernible from spectroscopic data alone.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Macrolides , Magnetic Resonance Spectroscopy , Micromonospora/metabolism , Molecular Structure , StereoisomerismABSTRACT
In the course of screening with the mixed lymphocyte reaction, a new inhibitor of protein kinase C with immunosuppressive activity was isolated from the fermentation broth and mycelia of Streptomyces sp. AB 1869R-359. Although certain similarities exist, this strain is morphologically and physiologically distinct from other reported producers of staurosporine-related compounds. We have found that this strain produces relatively high levels of staurosporine and the new minor compound MLR-52, which possesses the indolo[2,3-a]carbazole chromophore of staurosporine, but differs in the substitution pattern of the sugar moiety. Their structures have been elucidated by mass and NMR spectra. MLR-52 has been shown to inhibit the enzymatic activity of protein kinase C and the murine mixed lymphocyte reaction.
Subject(s)
Alkaloids , Immunosuppressive Agents , Protein Kinase C/antagonists & inhibitors , Alkaloids/chemistry , Alkaloids/isolation & purification , Alkaloids/metabolism , Alkaloids/pharmacology , Animals , Culture Media , Female , Fermentation , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/isolation & purification , In Vitro Techniques , Lymphocyte Culture Test, Mixed , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Staurosporine/analogs & derivatives , Streptomyces/metabolismABSTRACT
A family of novel compounds has been detected and isolated following an assay for the attenuation of multiple drug resistance in tumor cells from the fermentation broth and mycelia of a strain of Aspergillus fischeri which we have designated var. brasiliensis. The structures of three components were determined employing 1-D and 2-D homonuclear and heteronuclear NMR spectroscopy and mass spectrometry. The structure of 5-N-acetylardeemin was confirmed by single crystal X-ray diffraction. These compounds are most closely structurally related to asperlicin E1).
Subject(s)
Antibiotics, Antineoplastic/isolation & purification , Aspergillus/chemistry , Heterocyclic Compounds/isolation & purification , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/pharmacology , Drug Resistance, Microbial , Heterocyclic Compounds/chemistry , Heterocyclic Compounds/pharmacology , Humans , Magnetic Resonance Spectroscopy , Pyrimidinones/chemistry , Pyrimidinones/isolation & purification , Pyrimidinones/pharmacology , Tumor Cells, Cultured/drug effectsABSTRACT
A novel complex of antifungal and immunosuppressant compounds has been isolated from the fermentation broth and mycelia of two strains of Streptomyces diastatochromogenes. The structures of eight related components were determined employing 1D and 2D homonuclear and the heteronuclear NMR spectroscopy and mass spectrometry. These structures represent the first reported spiroketal 24-membered macrolide natural products related to the common 26-membered oligomycins.
