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K Bock

Publications and source records attributed to K Bock.

At least 37 records · Page 2Linked to original sources
PubMed1997

Topological photoaffinity labeling of the rabbit ileal Na+/bile-salt-cotransport system.

For the investigation of the topology of the rabbit ileal Na+/bile-salt-cotransport system, composed of a 93-kDa integral membrane protein and a peripheral 14-kDa bile-acid-binding protein (ILBP), we have synthesized photolabile dimeric bile-salt-transport inhibitors (photoblockers), G1-X-G2, where two bile acid moieties (G1 and G2) are tethered together via a spacer, X, and where one of the two bile acid moieties carries a photoactivatable group. These photoblockers specifically interact with the ileal Na+/bile-salt-cotransport system as demonstrated by a concentration-dependent inhibition of [3H]cholyltaurine uptake by rabbit ileal brush-border membrane vesicles and by inhibition of photolabeling of the 93-kDa and 14-kDa bile-salt-binding proteins by 7,7-azo and 3,3-azo derivatives of cholyltaurine. Ileal bile-salt uptake was specifically inhibited by the photoblockers, which were not taken up themselves by the small intestine as demonstrated by in vivo ileal perfusion. Dependent on the photoblocker used several polypeptides in the molecular-mass range of 14-130 kDa were labeled. The cytoplasmically attached 14-kDa ILBP was significantly labeled only by inhibitors that are photoactivatable in bile acid moiety G1, suggesting that during binding and translocation of a bile-salt molecule by the ileal bile-salt-transport system the steroid nucleus gets access to the cytoplasmic site of the ileal brush-border membrane first. Photoaffinity labeling in the frozen state with the transportable 3,3-azo and 7,7-azo derivatives of cholyltaurine revealed a time-dependent increase in the extent of labeling of the 14-kDa and 93-kDa proteins, suggesting a labeling of these proteins from the cytoplasmic site of the ileal brush-border membrane. By photoaffinity labeling in the frozen state with the various photoblockers time-dependent changes in the extent of photoaffinity labeling of bile-salt-binding proteins were observed, demonstrating the possibility of topological analysis of the rabbit ileal Na+/bile-salt-cotransport system.

Affinity Labels↗
PubMed1997

Synthesis and characterisation of highly glycosylated glycopeptides with Tn-antigenic structures corresponding to human glycophorin AN.

Two highly glycosylated O-glycopeptides corresponding to human glycophorin AN with Tn-antigenic structures were synthesised. The first glycopeptide has two glycosylated clusters with three and six adjacent 2-acetamido-2-deoxy-D-galactose (GalNAc) glycosylation sites and represents the N-terminal octadecapeptide from Leu-1 to Lys-18. The second glycopeptide, a decapeptide from His-9 to Lys-18, contains as a compact cluster six adjacent GalNAc glycosylation sites. The solid phase synthesis was realised by using the carbohydrate-containing building blocks Fmoc-Ser(Ac3GalN3)-Pfp and Fmoc-Thr(Ac3GalN3)-Pfp. The synthesised substances were characterised by NMR spectroscopic techniques. The main techniques used were homonuclear TOCSY and NOESY as well as HMQC and HMBC for 13C,1H correlations.

Amino Acid Sequence↗
PubMed1997

The structure of the carbohydrate backbone of the lipopolysaccharide from Acinetobacter strain ATCC 17905.

The structure of the carbohydrate backbone of the lipopolysaccharide from Acinetobacter strain ATCC 17905 was studied. After deacylation of the lipopolysaccharide, a mixture of two compounds (ratio approximately 2:1) was isolated by high-performance anion-exchange chromatography, the structures of which were determined by NMR spectroscopy and electrospray-mass spectrometry as [STRUCUTRE IN TEXT] [Sug, 3-deoxy-D-manno-2-octulopyranosonic acid (Kdo) in oligosaccharide 1 (major portion) and D-glycero-D-talo-2-octulopyranosonic acid (Ko) in oligosaccharide 2 (minor portion)]. All monosaccharide residues also possess the D-configuration and are present in the pyranose form.

Acinetobacter↗
PubMed1997

Constrained glycopeptide ligands for MPRs. Limitations of unprotected phosphorylated building blocks.

A new methodology for the synthesis of cyclic and phosphorylated glycopeptide templates was developed. First, fully protected building blocks containing mannose and mannose disaccharides with bis-trichloroethyl phosphate on Fmoc-Thr-OPfp were synthesized. These were used in solid-phase assembly through side chain anchoring of glycosylated hexa- and octa-peptides protected at the C-terminal carboxylate as the allyl ester. Selective allyl ester cleavage and head-to-tail cyclization under pseudodilution conditions gave a high yield of pure cyclic peptide templates. Unprotected phosphate in the building block was evaluated as an alternative to the problematic trichloroethyl group. It was found that one unprotected phosphate is readily incorporated, whereas the second unprotected phosphorylated building block react very slowly due to electrostatic repulsion in the solid-phase synthesis. For comparison with previous binding studies modified glycopeptide templates containing only phosphorylated mannose monosaccharides or templates modified in the peptide part were synthesized. All the structures were tested for their binding to the mannose 6-phosphate receptor, and it was found that although mannose disaccharides are required for optimal interaction, the detailed structure of the peptide template has a strong influence on binding to the receptor. The restricted conformations of the cyclic peptides decreased the binding considerably.

Chromatography, High Pressure Liquid↗
PubMed1997

Structural requirements of synthetic oligosaccharides to bind monoclonal antibodies against Chlamydia lipopolysaccharide.

Monoclonal antibodies were generated against a synthetic glycoconjugate containing the trisaccharide alpha-Kdo-(2-->8)-alpha-Kdo-(2-->4)-alpha-Kdo (Kdo, 3-deoxy-D-manno-2-octulopyranosonic acid) which represents the genus-specific epitope of the lipopolysaccharide from the obligatory intracellular human pathogen Chlamydia. Antibodies of all immunoglobulin G isotypes were obtained and characterized by enzyme immunobinding and inhibition assays using the immunizing antigen as well as chemically synthesized derivatives of the Kdo trisaccharide. The latter contained (1) one of the three residues in beta- instead of alpha-linkage, (2) a Kdo residue the carboxyl group of which had been reduced to a CH2OH group (Kdo(C1-red)), or (3) changing the linkage of the terminal Kdo from 2-->8 to 2-->4. Only one compound, namely, alpha-Kdo-(2-->8)-alpha-Kdo(C1-red)-(2-->4)-alpha-Kdo exhibited binding to and inhibition of Kdo trisaccharide-specific antibodies, whereas all other compounds were not active. Structural and conformational investigations using NMR spectroscopy at high field on the allyl glycosides of the oligosaccharides 6-12 confirmed the conformational similarities between those structures 4, 5, and 10 which were able to bind to the antibodies investigated.

Animals↗
PubMed1997

That's the way the cookie bounces: syntactic and semantic components of experimentally elicited idiom blends.

Idioms are sometimes viewed as unitized phrases with interpretations that are independent of the literal meanings of their individual words. In three experiments, the nature of idiom representation was explored with a speech-error elicitation task. In the task, speakers briefly viewed paired idioms. After a short delay they were probed to produce one of the two idioms, and their production latencies and blend errors were assessed. The first experiment showed greater interference between idioms with the same syntactic structure, demonstrating that idiom representations contain syntactic information. The second experiment indicated that the literal meaning of an idiom is active during production. These syntactic and literal-semantic effects on idiom errors argue against a representation of idioms as noncomponential lexicalized phrases. In the final experiment, no differences were found between decomposable and nondecomposable idioms, suggesting that the lexical representation of these two types of idioms is the same.

Adult↗
PubMed1996

The extracellular polysaccharide of Pichia (Hansenula) holstii NRRL Y-2448: the structure of the phosphomannan backbone.

The phosphomannan core of the exopolysaccharide of Pichia (Hansenula) holstii NRRL Y-2448 was isolated after hydrolytic removal of the oligosaccharide phosphate side-chains. The core polysaccharide and its dephosphorylated derivative were subjected to extensive 1D and 2D NMR spectroscopy which yielded information on the linkage sites and on the sequence of the mannosyl residues in the major oligosaccharide repeating unit. The most probable structure for the repeating unit was -[6-O-PO3H2-alpha-D-Man-(1-->3)-alpha-D-Man-(1-->2)-alpha-D-Man-(1 -->2)]-alpha-D-Man-(1-->6)-[alpha-D-Man-(1-->2)]-alpha-D-Man-(1-->6)-. A semiquantitative conformational analysis was performed by Monte Carlo simulations and the result was confirmed by comparison with the experimentally determined NMR data. The distance distribution for the phosphate groups was determined from the modeling and was found to cover the expected range of distances for phosphorylated high-mannose oligosaccharides.

Carbohydrate Sequence↗
PubMed1996

Synthesis and structural studies of branched 2-linked trisaccharides related to blood group determinants.

A series of trisaccharide glycosides, Fuc-(1 reversible 2)-beta-Gal-(1 reversible 3)-beta-X-OMe (X = GlcNAc, Glc, 2-deoxy-Glc) related to the blood group determinant Le(d) have been synthesised both as their alpha- and beta-Fuc anomers together with the component disaccharide starting compounds. The conformational properties of the six trisaccharides together with their parent disaccharides have been investigated by NMR spectroscopy (proton and carbon chemical shifts and proton NOEs) in combination with computer modeling using the Monte Carlo approach and the HSEA force field using the GEGOP programme. The interaction between the terminal fucose unit and the reducing unit was probed by substitution of bulky NAc group with hydroxyl and deoxy substituents, respectively. Compounds with severe steric interactions were identified by the non-additivity of their carbon chemical shifts. This was subsequently confirmed by the detailed conformational assessment by NOE spectroscopy and computer modeling. The most severe contacts arose in the alpha-L-Fuc derivatives, whereas the beta-linked L-Fuc derivatives only in one case exhibit severe steric interaction as probed by the NMR parameters.

Carbohydrate Conformation↗
PubMed1996

Glycopeptide mimics of mammalian Man9GlcNAc2. Ligand binding to mannan-binding proteins (MBPs).

A novel and simple approach for rational design of oligosaccharide mimics has been developed. Mammalian high-mannose triantennary structure Man9GlcNac2 has been subjected to molecular modelling using the NMR data available on structural fragments of the oligosaccharide. The analysis indicated four different low energy conformations, and the spatial arrangement of terminal disaccharides of the oligosaccharide antennae were stimulated with glycopeptides carrying disaccharides by applying weak constraints between the saccharide parts in MD-simulations on a large array of tri- to octaglycopeptides. The five glycopeptides exhibiting the best fit with the four minimum energy confirmations of the oligosaccharide were synthesized by solid phase glycopeptide assembly using glycosylated fluoren-9-ylmethyloxycarbonyl-amino acid-O-pentafluorophenyl esters as building blocks. The glycan was acyl protected alpha-D-Man-(1-->2)-alpha-D-Man and Ser, Thr and Hyp were the glycosylated amino acids. The deprotected and purified glycopeptides were subjected to NMR analysis for characterization, and in order to investigate the cis-trans isomerism of the carbimide bonds to Hyp. The glycopeptides were tested for their ability to inhibit binding of mannan-binding protein to mannan from Saccharomyces cerevisiae. They were found to be weak inhibitors showing no indication of multivalent interaction with the mannan-binding protein.

Carbohydrate Conformation↗
PubMed1995

Transferred nuclear Overhauser enhancement experiments show that the monoclonal antibody strep 9 selects a local minimum conformation of a Streptococcus group A trisaccharide-hapten.

Transferred nuclear Overhauser enhancement (TRNOE) experiments have been performed to investigate the bound conformation of the trisaccharide repeating unit of the Streptococcus Group A cell-wall polysaccharide. Thus, the conformations of propyl 3-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-2-O-(alpha-L-rhamnopyran osyl)- alpha-L-rhamnopyranoside [C(A')B] (1) as a free ligand and when complexed to the monoclonal antibody Strep 9 were examined. Improved insights about the conformational preferences of the glycosidic linkages of the trisaccharide ligand showed that the free ligand populates various conformations in aqueous solution, thus displaying relatively flexible behavior. The NOE HNAc-H2A', which was not detected in previous work, accounts for a conformation at the beta-(1-->3) linkage with a phi angle of approximately 180 degrees. Observed TRNOEs for the complex are weak, and their analysis was further complicated by spin diffusion. With the use of transferred rotating-frame Overhauser enhancement (TRROE) experiments, the amount of spin diffusion was assessed experimentally, proving that all of the observed long-range TRNOEs arose through spin diffusion. Four interglycosidic distances, derived from the remaining TRNOEs and TRROEs, together with repulsive constraints, derived from the absence of TRROE effects, were used as input parameters in simulated annealing and molecular mechanics calculations to determine the bound conformation of the trisaccharide. Complexation by the antibody results in the selection of one defined conformation of the carbohydrate hapten. This bound conformation, which is a local energy minimum on the energy maps calculated for the trisaccharide ligand, shows only a change from a +gauche to a -gauche orientation at the psi angle of the alpha-(1-->2) linkage when compared to the global minimum conformation. The results infer that the bound conformation of the Streptococcus Group A cell-wall polysaccharide is different from its previously proposed solution structure (Kreis et al., 1995).

Antibodies, Monoclonal↗
PubMed1995

The structure of the lipid A-core region of the lipopolysaccharides from Vibrio cholerae O1 smooth strain 569B (Inaba) and rough mutant strain 95R (Ogawa).

The lipopolysaccharides (LPS) from Vibrio cholerae 95R, a rough mutant strain of O1 V. cholerae 162 (Ogawa), and from smooth O1 V. cholerae 569B (Inaba) were de-O-acylated. In each case, one part of the products was treated with 48% aqueous HF which removed the phosphoryl and fructose residues, then reduced, de-N-acylated, and N-acetylated. Another part was de-N-acylated by treatment with hot KOH. The products of both degradation pathways were separated by high-performance anion-exchange chromatography. The major dephosphorylated and defructosylated product 1 was obtained in pure form, whereas the minor products 2 and 3 were eluted as a mixture, as were, from the second degradation, the phosphorylated oligosaccharides 4 (major product) and 5 (minor product). No phosphorylated component corresponding to oligosaccharide 3 could be identified by NMR spectroscopy in the latter mixture. The following structures of oligosaccharides 1-5 were established on the basis of monosaccharide and methylation analyses, Smith degradation, and 1H- and 13C-NMR investigations (correlated, total correlated, NOE and heteronuclear correlation spectroscopy; all sugars are present as alpha-D-pyranoses except where indicated otherwise; Hep, L-glycero-D-manno-heptose; Kdo, 3-deoxy-D-manno-2-octulosonic acid). [formula: see text] In the untreated lipopolysaccharide, the amino group of the non-reducing terminal glucosamine residue is not substituted.

Carbohydrate Sequence↗
PubMed1995

The structures of oligosaccharide bisphosphates isolated from the lipopolysaccharide of a recombinant Escherichia coli strain expressing the gene gseA [3-deoxy-D-manno-octulopyranosonic acid (Kdo) transferase] of Chlamydia psittaci 6BC.

The lipopolysaccharide from the recombinant strain Escherichia coli F515-140 containing the cloned gene gseA [3-deoxy-D-manno-octulopyranosonic acid (Kdo) transferase] from Chlamydia psittaci 6BC was isolated and sequentially de-O-acylated and de-N-acylated. The products were separated by high-performance anion-exchange chromatography into three fractions, two of which contained a single compound. Their structures were elucidated by high-field NMR spectroscopy as alpha-Kdo-(2-->4)-alpha-Kdo-(2-->6)-beta-D-GlcN-(1-->6)-alpha-D-GlcN 1,4'-P2 (compound 1) (tetrasaccharide bisphosphate) [Holst, O., Broer, W., Thomas-Oates, J. E., Mamat, U. & Brade, H. (1993) Eur. J. Biochem. 214, 703-710] and alpha-Kdo-(2-->4)-[alpha-Kdo-(2-->8)-]-alpha-Kdo-(2-->4)-alpha-Kdo- (2-->6)-beta-D-GlcN-(1-->6)-alpha-D-GlcN 1,4'-P2 (compound 4) (hexasaccharide bisphosphate). The third fraction comprised two pentasaccharide bisphosphates, which could be separated by affinity chromatography using an immobilized monoclonal antibody specific for the trisaccharide alpha-Kdo-(2-->8)-alpha-Kdo-(2-->4)-alpha-Kdo. The bound fraction was identified as alpha-Kdo-(2-->8)-alpha-Kdo-(2-->4)-alpha-Kdo-(2-->6)-beta-D- GlcN-(1-->6)-alpha-D-GlcN 1,4'-P2 (compound 2) [Holst, O., Broer, W., Thomas-Oates, J. E., Mamat, U. & Brade, H. (1993) Eur. J. Biochem. 214, 703-710], whereas the unbound fraction was identified as alpha-Kdo-(2-->4)-alpha-Kdo-(2-->4)-alpha-Kdo-(2-->6)-beta-D-GlcN-(1-->6 )- alpha-D-GlcN 1,4'-P2 (compound 3). This novel Kdo tetrasaccharide extends our knowledge on multifunctional Kdo transferases.

Carbohydrate Sequence↗
PubMed1995

Synthesis of the glycosyl amino acids N alpha-Fmoc-Ser[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D-GalN3p]-OPfp and N alpha-Fmoc-Thr[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D-GalN3p]-OPfp and the application in the solid-phase peptide synthesis of multiply glycosylated mucin peptides with Tn and T antigenic structures.

Two new glycosyl amino acids N alpha-Fmoc-Ser[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D-GalN3p]-+ ++OPfp and N alpha-Fmoc-Thr[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D-GalN3p]-+ ++OPfp were synthesized. Glycosylation of N alpha-Fmoc-Ser-OPfp or N alpha-Fmoc-Thr-OPfp with protected beta-D-Gal-(1-->3)-D-GalN3 donors afforded the glycosyl amino acids containing an activated C-terminus which could be utilized directly for solid-phase glycopeptide synthesis. The transformation of the 2-azido group into the acetamido derivative was achieved quantitatively at the end of the synthesis by treatment of the polymer-bound glycopeptide with thioacetic acid. The versatility of this strategy was demonstrated by the assembly of eight triply glycosylated mucin peptides which were synthesized simultaneously by multiple column techniques. The glycopeptides were prepared in order to investigate the substrate specificity of a galactosyltransferase.

Amino Acid Sequence↗
PubMed1995

[Standardization and quality assurance exemplified by tinnitus].

Quality management will become another discipline for intensive care and research for the physician. Therefore, the first step in this process will be the need for standardised evaluation criteria and case record forms for documentation, leading to effective quality assessment and control. Only this approach may promote our attempts to improve the quality of patient care. Tinnitus is, due to the lack of objective measurable parameters and a missing rational basis of therapy, up to now a "crux medicorum" for every involved person. In this paper we reproduce a case record form and a patient's questionnaire for patients suffering from tinnitus. The presented forms are based on a consensus conference concerning the evaluation of treatment regimens held at the Fourth International Tinnitus Seminar in Bordeaux in August 1991. Epidemiological data, collected with this questionnaire, are presented and analysed. In conclusion, the presented case record form will lead to a standardised evaluation of symptoms according to tinnitus and improve our understanding of concomitant disturbances in tinnitus sufferers. Furthermore, this form of evaluation and documentation will produce comparable data in different centres allowing a pooling of patients data and history. A comparison of clinical trials in which the items are collected by the procedure shown here will be facilitated and lead us to a new understanding in determining the causes of the disease and the outcome of different therapeutic regimens.

Adolescent↗
PubMed1994

Bile acid derived HMG-CoA reductase inhibitors.

The target organ for HMG-CoA reductase inhibitors to decrease cholesterol biosynthesis in hypercholesterolemic patients is the liver. Since bile acids undergo an enterohepatic circulation showing a strict organotropism for the liver and the small intestine, the structural elements of an inhibitor for HMG-CoA reductase were combined with those for specific molecular recognition of a bile acid molecule for selective uptake by hepatocytes. Either, the HMG-CoA reductase inhibitors HR 780 and mevinolin were covalently attached to 3 xi-(omega-aminoalkoxy)-7 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oic acids to obtain bile acid prodrugs, or the side chain of bile acids at C-17 was replaced by 3,5-dihydroxy-heptanoic acid--a structural element essential for inhibition of HMG-CoA reductase--to obtain hybrid bile acid: HMG-CoA reductase inhibitors. The prodrugs could, as expected, not inhibit rat liver HMG-CoA reductase to a significant extent, whereas the hybrid inhibitors showed a stereospecific inhibition of HMG-CoA reductase from rat liver microsomes with an IC50-value of 0.7 microM for the most potent compound S 2467 and 6 microM for its diastereomere S 2468. Uptake measurements with isolated rat hepatocytes and ileal brush-border membrane vesicles from rabbit small intestine revealed a specific interaction of both classes of bile acid-derived HMG-CoA reductase inhibitors with the hepatocyte and ileocyte bile acid uptake systems. Photoaffinity labeling studies using 3-azi- or 7-azi-derivatives of taurocholate with freshly isolated rat hepatocytes or rabbit ileal brush-border membrane vesicles revealed a specific interaction of bile acid derived HMG-CoA reductase inhibitors with the respective putative bile acid transporters in the liver and the ileum demonstrating the bile acid character of these derivatives, both for the prodrugs and the hybrids. Cholesterol biosynthesis in Hep G2 cells was inhibited by the bile acid prodrugs with IC50-values in the range of 68 nM to 600 nM compared to 13 nM for HR 780 and 130 nM for mevinolin. Among the hybrid inhibitors, S 2467 was the most active compound with an IC50-value of 16 microM compared to 55 microM for its diastereomere S 2468. Preliminary in vivo experiments showed an inhibition of hepatic cholesterol biosynthesis after oral dosage only with prodrugs such as S 3554, whereas the hybrid molecules were inactive after oral application.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Isolation and structural analysis of oligosaccharide phosphates containing the complete carbohydrate chain of the lipopolysaccharide from Vibrio cholerae strain H11 (non-O1).

For the first time, an oligosaccharide has been prepared comprising the lipid A backbone, the core oligosaccharide and one repeating unit of the O-specific polysaccharide (O-chain) of a lipopolysaccharide. Lipopolysaccharide from Vibrio cholerae strain H11 (non-O1) was deacylated and the products were separated by high-performance anion-exchange chromatography. Major fractions were a hexadecasaccharide trisphosphate 1, representing the core-lipid A oligosaccharide substituted by one modified repeating unit of the O-antigenic polysaccharide, a dodecasaccharide trisphosphate 2 and an undecasaccharide trisphosphate 3, representing the core-lipid A region. Oligosaccharide 1 originated from beta-elimination upon alkaline hydrolysis of alpha-galacturonic acid of the O-chain; oligosaccharides 2 and 3 were most likely obtained from naturally occurring lipopolysaccharide species carrying no O-chain. The structures of these compounds were elucidated on the basis of monosaccharide composition, and NMR investigations comprising correlation spectroscopy, total correlation spectroscopy and nuclear Overhauser enhancement spectroscopy experiments, as well as heteronuclear 13C, 1H correlation spectroscopy. The structures are as follows: [formula: see text] where R is beta-L-threo-hex-4-enuronopyranosyl-(1-4)-alpha-Neu-(2-3)-beta-Gal A-(1-3)- beta-QuiN-(1-4)-beta-Sedf-(2- in 1, beta-Sedf-(2- in 2, and H in 3. Where not stated otherwise, sugars are pyranoses of the D-series. Hep is L-glycero-D-manno-heptose, QuiN is 2-amino-2,6-dideoxy-glucose, Kdo is 3-deoxy-D-manno-2-octulosonic acid, Sed is D-altro-heptulose and GalA is galacturonic acid.

Carbohydrate Sequence↗
PubMed1994

Synthesis and biological activity of bile acid-derived HMG-CoA reductase inhibitors. The role of 21-methyl in recognition of HMG-CoA reductase and the ileal bile acid transport system.

To increase hepatoselectivity of HMG-CoA reductase inhibitors by using the specific bile acid transport systems, deoxycholic acid-derived inhibitors 9 and 11 have been synthesized, on the basis of the concept of combining in one molecule structural requirements for specific inhibition of the HMG-CoA reductase and specific recognition by the ileal bile acid transport system. The 1-methyl-3-carboxylpropyl subunit of deoxycholic acid was replaced by the 3,5-dihydroxyheptanoic acid lactone of lovastatin, and position 12-OH was esterified with 2-methylbutyric acid. Compounds 9 and 11 were evaluated for their inhibitory activity on rat liver HMG-CoA reductase, cholesterol biosynthesis in HEP G2 cells, and [3H]taurocholate uptake in rabbit brush border membrane vesicles and compared with methyl derivatives 8 and 10. The steroidal 21-CH3 group affects both activity on HMG-CoA reductase and recognition by the ileal bile acid transport system.

Androstanols↗