Synthesis of alpha-heterosubstituted nitrosamines. Novel test substances for cancer and mutagenesis research?
Explore the source record for details and available documents.
Carcinogens↗
Biomedical subjects
D Seebach
Publications and source records attributed to D Seebach.
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of monodisperse cPHAs, the oligo(3-hydroxyalkanoates), with emphasis on the butyrates (OHB); we report hitherto unpublished results on the enzymatic degradation of cPHB and PMA, on a new analytical method for HB/HV detection in biological samples, and on OHB-mediated Ca2+ transport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↗
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↗