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Biomedical subjects

D Seebach

Publications and source records attributed to D Seebach.

26 records · Page 2Linked to original sources
PubMed1995

Alpha-methyl-proline restores normal levels of bone collagen Type I synthesis in ovariectomized rats.

Collagen type I is the major protein of bone matrix and significantly reduced in osteoporosis. We tested the effect of alpha - methyl - proline on collagen synthesis in the model of the ovariectomized rat. Collagen synthesis was studied at the transcriptional level using Northern and dot blotting and at the protein level using hydroxyproline determination and a specific dye binding collagen assay. Alpha - methyl- proline treatment significantly increased collagen synthesis as compared to untreated ovariectomized and estradiol treated ovariectomized rats and restored collagen synthesis to levels of sham operated rats. Proline analogues were described to stimulate procollagen synthesis at the transcriptional level, however, if incorporated, lead to negative collagen production due to rapid intracellular degradation of the deficient collagen. Our synthesized analogue is not being incorporated, thus not interfering with collagen conformation and can therefore induce collagen production.

Animals↗
PubMed1995

Biodegradation of cyclic and substituted linear oligomers of poly(3-hydroxybutyrate).

Cyclic oligo(3-hydroxybutyrate), oligo(3-HB), was synthesized and purified, resulting in oligolides that contained three to seven (R)-3-hydroxybutyrate units (triolides up to heptolides). In addition, linear 3-HB octamers obtained as either tert-butyl or methyl esters were substituted with different end groups at the hydroxy end. The hydroxy terminus was replaced by either a benzyloxy, trifluoroacetoxy, crotonyloxy (S)-3-hydroxybutyryloxy, or fluorenylmethylcarbonyloxy (FMOC) group. P(3-HB) hairpin loops occurred on the surface of certain regions of the polymer, especially of lamellar crystallites. Cyclic 3-HB oligomers provide a model system for these loops. It is assumed that they provide attachment points for the depolymerizing enzymes. All of the (R)-oligolides tested were degraded except the (R)-triolide. Triolides were not degraded, suggesting that enzymatic attack was prevented presumably by steric hindrance on the rigid ring system. Unsubstituted linear octamers were degraded. Biodegradation was prevented when the hydroxy terminus was protected by the FMOC group, but was not dependent on a free hydroxy terminal group; all other protecting groups did not prevent degradation. Substitution of the carboxy end of a methyl or tert-butyl ester group did not influence biodegradation.

Biodegradation, Environmental↗
PubMed1994

Isolation and 1H-NMR spectroscopic identification of poly(3-hydroxybutanoate) from prokaryotic and eukaryotic organisms. Determination of the absolute configuration (R) of the monomeric unit 3-hydroxybutanoic acid from Escherichia coli and spinach.

Trace amounts of poly[(R)-3-hydroxybutanoate] were isolated from competent Escherichia coli, spinach, bovine serum albumin, beef heart mitochondria, and aortal tissues, all sources in which it is not accumulated as storage material. Its identity was in all cases proved by 1H-NMR spectroscopy. In some runs, the poly[(R)-3-hydroxybutanoate] isolated from competent E. coli also contained some 3-hydroxyvalerate, an observation confirmed by 1H-NMR spectroscopy and gas chromatography. The absolute configuration of the polymers isolated from E. coli and spinach was shown to be (all-R) by gas chromatography on chiral columns.

Animals↗
PubMedDate not supplied

Detection, synthesis, structure, and function of oligo(3-hydroxyalkanoates): contributions by synthetic organic chemists.

Two types of the biological macromolecules poly(R-3-hydroxyalkanoates) have been identified: the high-molecular-weight microbial storage material (sPHA) and a short-chain variety, consisting of butyrate and valerate residues, complexed with other biomacromolecules such as calcium polyphosphate or proteins (cPHB/PHV). While sPHA has attracted, and still enjoys, a lot of attention from numerous scientists around the world, research on cPHB and the structurally and functionally related polymalate (PMA) is still in its infancy. In this article, we present a review on the chemical synthesis, structure, function and interactions of monodisperse cPHAs, the oligo(3-hydroxyalkanoates), with emphasis on the butyrates (OHB); we report hitherto unpublished results on the enzymatic degradation of cPHB and PMA, on a new analytical method for HB/HV detection in biological samples, and on OHB-mediated Ca2+ transport through phospholipid bilayers of artificial vesicles; finally, we discuss possible mechanisms of ion transport through cell membranes, as caused by cPHB. The speculative--and provocative--question is asked whether the structurally simple PHAs may have evolved as storage materials and amphiphilic macromolecules before poly-peptides, -saccharides, and -nucleic acids, in the history of life, or under prebiotic conditions.

Animals↗
PubMedDate not supplied

Structure-based design of nonnatural ligands for the HLA-B27 protein.

X-ray studies as well as structure-activity relationships indicate that the central part of class I MHC-binding nonapeptides represents the main interaction site for a T cell receptor. In order to rationally manipulate T cell epitopes, several nonpeptidic spacer have been designed from the X-ray structure of a MHC-peptide complex and substituted for the T cell receptor-binding part of several antigenic peptides. The binding of the modified epitopes to the HLA-B*2705 protein was studied by an in vitro stabilisation assay and the thermal stability of all complexes examined by circular dichroism spectroscopy. Depending on their chemical nature and length, the introduced spacers may be classified into two categories. Monofunctional spacers (11-amino undecanoate, (R)-3-hydroxybutyrate trimer) simply link two anchoring peptide positions (P3 and P9) but loosely contact the MHC binding groove, and thus decrease more or less the affinity of the altered epitopes to HLA-B*2705. Bifunctional spacers ((R)-3-hydroxybutyrate and beta-homoalanine combinations) not only bridges the two distant anchoring amino acids but also strongly interact with the binding cleft and lead to an increase in binding to the MHC protein. The presented modified ligands constitute interesting tools for perturbing the T cell response to the parent antigenic peptide.

Affinity Labels↗