MARINE STEROLS: VIII. IN VIVO TRANSFORMATIONS OF THE STEROL SIDE CHAIN BY A CLAM

1961 ◽  
Vol 39 (3) ◽  
pp. 505-509 ◽  
Author(s):  
U. H. M. Fagerlund ◽  
D. R. Idler
Keyword(s):  
Sterol Fraction ◽  
Side Chain ◽  
Saxidomus Giganteus

Analysis of the ozonolysis products of a sterol fraction obtained from clams (Saxidomus giganteus) injected with cholesterol-26-C14 has demonstrated that these molluscs are able to introduce unsaturation into the cholesterol side chain at C-22 and C-25.

In vivo modulated N -acyl side chain of N -acetylneuraminic acid modulates the cell contact-dependent inhibition of growth

FEBS Letters ◽  
1996 ◽  
Vol 395 (2-3) ◽  
pp. 170-173 ◽  
Author(s):  
J.Raimund Wieser ◽  
Anja Heisner ◽  
Peer Stehling ◽  
Franz Oesch ◽  
Werner Reutter
Keyword(s):  
Side Chain ◽  
Cell Contact ◽  
Acetylneuraminic Acid ◽  
Inhibition Of Growth ◽  
Acyl Side Chain ◽  
Dependent Inhibition

MARINE STEROLS: IX. BIOSYNTHESIS OF 24-METHYLENECHOLESTEROL IN CLAMS

1961 ◽  
Vol 39 (9) ◽  
pp. 1347-1355 ◽  
Author(s):  
U. H. M. Fagerlund ◽  
D. R. Idler
Keyword(s):  
Digestive Gland ◽  
Saxidomus Giganteus

Clams (Saxidomus giganteus) are able to transform injected cholesterol-4-C14 into radioactive 24-methylenecholesterol in vivo. The highest rate of conversion was observed when the radioactive sterol was injected into the digestive gland. The findings suggest a possible pathway in the biosynthesis of C28-sterols and throw some light on the question of the origin of C28-sterols in lamellibranchs.

scholarly journals Mutant tryptophan aporepressors with altered specificities of corepressor recognition.

Genetics ◽  
1991 ◽  
Vol 128 (1) ◽  
pp. 29-35
Author(s):  
D N Arvidson ◽  
M Shapiro ◽  
P Youderian
Keyword(s):  
Dna Binding ◽  
Binding Pocket ◽  
Side Chain ◽  
Wild Type ◽  
Mutant Proteins ◽  
Naturally Occurring ◽  
Repressor Complex ◽  
Genes Encoding ◽  
Active Repressor

Abstract The Escherichia coli trpR gene encodes tryptophan aporepressor, which binds the corepressor ligand, L-tryptophan, to form an active repressor complex. The side chain of residue valine 58 of Trp aporepressor sits at the bottom of the corepressor (L-tryptophan) binding pocket. Mutant trpR genes encoding changes of Val58 to the other 19 naturally occurring amino acids were made. Each of the mutant proteins requires a higher intracellular concentration of tryptophan for activation of DNA binding than wild-type aporepressor. Whereas wild-type aporepressor is activated better by 5-methyltryptophan (5-MT) than by tryptophan, Ile58 and other mutant aporepressors prefer tryptophan to 5-MT as corepressor, and Ala58 and Gly58 prefer 5-MT much more strongly than wild-type aporepressor in vivo. These mutant aporepressors are the first examples of DNA-binding proteins with altered specificities of cofactor recognition.

Subtle changes in network composition impact the biodistribution and tumor accumulation of nanogels

2018 ◽  
Vol 54 (83) ◽  
pp. 11777-11780 ◽  
Author(s):  
Ilona Zilkowski ◽  
Ioanna Theodorou ◽  
Krystyna Albrecht ◽  
Frederic Ducongé ◽  
Jürgen Groll
Keyword(s):  
Breast Tumor ◽  
Tumor Targeting ◽  
Near Infrared ◽  
Side Chain ◽  
Human Breast ◽  
Human Breast Tumor ◽  
Tumor Xenografts ◽  
Network Composition ◽  
Tumor Accumulation

We studied the effect of subtle changes in side-chain chemistry and labelling with near infrared fluorophores of nanogels (NGs) prepared from thiolated poly(glycidol) on in vivo biodistribution in mice bearing human breast tumor xenografts. Side chain chemistry as well as labelling clearly influenced tumor targeting and overall biodistribution.

scholarly journals d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B

2018 ◽  
Vol 115 (11) ◽  
pp. 2818-2823 ◽  
Author(s):  
Wei Tang ◽  
Zhengyan Guo ◽  
Zhenju Cao ◽  
Min Wang ◽  
Pengwei Li ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Carbon Chain ◽  
Side Chain ◽  
Hygromycin B ◽  
Nucleoside Antibiotics ◽  
Common Precursor ◽  
Encoding Genes ◽  
Poultry Farming

Seven-carbon-chain–containing sugars exist in several groups of important bacterial natural products. Septacidin represents a group of l-heptopyranoses containing nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. Hygromycin B, an aminoglycoside anthelmintic agent used in swine and poultry farming, represents a group of d-heptopyranoses–containing antibiotics. To date, very little is known about the biosynthesis of these compounds. Here we sequenced the genome of the septacidin producer and identified the septacidin gene cluster by heterologous expression. After determining the boundaries of the septacidin gene cluster, we studied septacidin biosynthesis by in vivo and in vitro experiments and discovered that SepB, SepL, and SepC can convert d-sedoheptulose-7-phosphate (S-7-P) to ADP-l-glycero-β-d-manno-heptose, exemplifying the involvement of ADP-sugar in microbial natural product biosynthesis. Interestingly, septacidin, a secondary metabolite from a gram-positive bacterium, shares the same ADP-heptose biosynthesis pathway with the gram-negative bacterium LPS. In addition, two acyltransferase-encoding genes sepD and sepH, were proposed to be involved in septacidin side-chain formation according to the intermediates accumulated in their mutants. In hygromycin B biosynthesis, an isomerase HygP can recognize S-7-P and convert it to ADP-d-glycero-β-d-altro-heptose together with GmhA and HldE, two enzymes from the Escherichia coli LPS heptose biosynthetic pathway, suggesting that the d-heptopyranose moiety of hygromycin B is also derived from S-7-P. Unlike the other S-7-P isomerases, HygP catalyzes consecutive isomerizations and controls the stereochemistry of both C2 and C3 positions.

MARINE STEROLS: VI. STEROL BIOSYNTHESIS IN MOLLUSCS AND ECHINODERMS

1960 ◽  
Vol 38 (1) ◽  
pp. 997-1002 ◽  
Author(s):  
U. H. M. Fagerlund ◽  
D. R. Idler
Keyword(s):  
Sterol Biosynthesis ◽  
Major Portion ◽  
Mytilus Californianus ◽  
Polar Zone ◽  
Pisaster Ochraceus ◽  
Saxidomus Giganteus

The in vivo incorporation of 2-C14-acetate into digitonin-precipitable material has been demonstrated in two molluscs, mussel (Mytilus californianus) and clam (Saxidomus giganteus). Clams are able to convert 11,14-C14-squalene into digitonin-precipitable material. When the azoylester of the material isolated from clams is chromatographed, the major portion of the radioactivity follows the least polar zone, which has previously been found to contain mainly monounsaturated Δ5-sterols.A starfish (Pisaster ochraceus) has been shown in vivo to convert ingested 4-C14-cholesterol to 7-cholestenol.

STEROID BIOSYNTHESIS IN VITRO BY A VIRILIZING SUPRARENAL TUMOUR

1963 ◽  
Vol 44 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Roversi G. D. ◽  
Polvani F. ◽  
Bompiani A. ◽  
Neher R.
Keyword(s):  
Adrenal Adenoma ◽  
Tumour Tissue ◽  
Side Chain ◽  
Steroid Biosynthesis ◽  
Before And After

ABSTRACT A case of virilizing adrenal adenoma is described. The tumour was incubated with progesterone-4-14C. In the extract the following steroids were identified chromatographically, in order of decreasing quantity and radioactivity: 17α-hydroxyprogesterone, androst-4-ene-3,17-dione, corticosterone (11β,21 -dihydroxy-pregn-4-ene-3,20-dione), cortisol (11β,17,21-trihydroxy-pregn-4-ene-3,20-dione) and 11-deoxycortisol. This indicates either an increase in 17α-hydroxylation and side chain split, or a partial blockage of 21-hydroxylation, or a combination of both in the tumour tissue. The absence of the 3β-hydroxy-dehydrogenase demonstrated histochemically in the tumour and the examination of the urinary 17-ketosteroids before and after removal of the neoplasm, suggested the same abnormal biosynthetic pattern in vivo with regard to the level of the endogenous Δ5-precursors.

MARINE STEROLS: VI. STEROL BIOSYNTHESIS IN MOLLUSCS AND ECHINODERMS

1960 ◽  
Vol 38 (9) ◽  
pp. 997-1002 ◽  
Author(s):  
U. H. M. Fagerlund ◽  
D. R. Idler
Keyword(s):  
Sterol Biosynthesis ◽  
Major Portion ◽  
Mytilus Californianus ◽  
Polar Zone ◽  
Pisaster Ochraceus ◽  
Saxidomus Giganteus

The in vivo incorporation of 2-C14-acetate into digitonin-precipitable material has been demonstrated in two molluscs, mussel (Mytilus californianus) and clam (Saxidomus giganteus). Clams are able to convert 11,14-C14-squalene into digitonin-precipitable material. When the azoylester of the material isolated from clams is chromatographed, the major portion of the radioactivity follows the least polar zone, which has previously been found to contain mainly monounsaturated Δ5-sterols.A starfish (Pisaster ochraceus) has been shown in vivo to convert ingested 4-C14-cholesterol to 7-cholestenol.

scholarly journals Pyridyl-Ala Modified Cyclic Hexapeptides: In-Vitro and In-Vivo Profiling for Oral Bioavailability

2019 ◽  
Vol 26 (3) ◽  
pp. 1383-1397 ◽  
Author(s):  
Thomas Vorherr ◽  
Ian Lewis ◽  
Joerg Berghausen ◽  
Felix Huth ◽  
Michael Schaefer ◽  
...  
Keyword(s):  
Amino Acid ◽  
Oral Bioavailability ◽  
Side Chain ◽  
Pyridyl Nitrogen ◽  
Oral Uptake ◽  
Cyclic Hexapeptides ◽  
Chain Interaction

Abstract We and others have been aiming at modifications to maintain or to enhance solubility while enabling permeability for cyclic hexapeptides. Especially, the 2-pyridyl-Ala modification was investigated, since in this case, the pyridyl-nitrogen is able to form an H-bond to the NH of the same residue. The hypothesis of a backbone side-chain interaction was demonstrated by NMR experiments, and further results obtained on a variety of pyridyl-Ala derivatives, studied systematically in the context of permeability, are presented in this contribution. Thus, this study sheds some more light on the pyridyl-Ala modification, which had been reported earlier. In addition to the in vitro profiling, the extent of oral bioavailability was assessed in rats. In principle, the pyridyl-Ala residue can be considered as an amino acid supporting oral uptake. Graphic Abstract

scholarly journals Synthesis, CYP24A1-Dependent Metabolism and Antiproliferative Potential against Colorectal Cancer Cells of 1,25-Dihydroxyvitamin D2 Derivatives Modified at the Side Chain and the A-Ring

2020 ◽  
Vol 21 (2) ◽  
pp. 642
Author(s):  
Magdalena Milczarek ◽  
Michał Chodyński ◽  
Anita Pietraszek ◽  
Martyna Stachowicz-Suhs ◽  
Kaori Yasuda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Cancer Cells ◽  
Biologically Active ◽  
Side Chain ◽  
Anticancer Properties ◽  
Colorectal Cancer Cells ◽  
Ht 29

Experimental data indicate that low-calcemic vitamin D derivatives (VDDs) exhibit anticancer properties, both in vitro and in vivo. In our search for a vitamin D analog as potential anticancer agent, we investigated the influence of chirality in the side chain of the derivatives of 1,25-dihydroxyergocalciferol (1,25D2) on their activities. In this study, we synthesized modified analogs at the side chain and the A-ring, which differed from one another in their absolute configuration at C-24, namely (24S)- and (24R)-1,25-dihydroxy-19-nor-20a-homo-ergocalciferols (PRI-5105 and PRI-5106, respectively), and evaluated their activity. Unexpectedly, despite introducing double-point modifications, both analogs served as very good substrates for the vitamin D-hydroxylating enzyme. Irrespective of their absolute C-24 configuration, PRI-5105 and PRI-5106 showed relatively low resistance to CYP24A1-dependent metabolic deactivation. Additionally, both VDDs revealed a similar antiproliferative activity against HT-29 colorectal cancer cells which was higher than that of 1,25D3, the major biologically active metabolite of vitamin D. Furthermore, PRI-5105 and PRI-5106 significantly enhanced the cell growth-inhibitory activity of 5-fluorouracil on HT-29 cell line. In conclusion, although the two derivatives showed a relatively high anticancer potential, they exhibited undesired high metabolic conversion.

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