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Biomedical subjects

D Brandenburg

Publications and source records attributed to D Brandenburg.

134 records · Page 8Linked to original sources
PubMedDate not supplied

Biological action and fate of photoaffinity-labelled insulin-receptor complexes.

Covalent linking of two photoactivatable insulin derivatives, B2-(2-nitro,4-azidophenylacetyl)-des-PheB1-insulin and B29-(2-nitro,4-azidophenylacetyl)-insulin to viable rat adipocytes gives a system, which contains a fixed stoichiometry between hormone and receptor. The biological signal of prolonged lipogenesis has been used to study several aspects of insulin binding and action: the role of the site of the crosslink between insulin and receptor, recognition of bound photoinsulin by anti-insulin antibodies, the half-life of the biologically active complex, the pH-dependence of the biological signal, and the possible role of internalization. Furthermore, the effect of trypsin on the insulin receptor, as well as the insulin-receptor complex, has been investigated and a refined model of the receptor is presented.

Adipose Tissue↗
PubMedDate not supplied

The subunit structure of the insulin receptor and molecular interactions with major histocompatibility complex antigens.

Insulin receptors were labeled with 125I-photoreactive insulin (specifically labeling alpha-subunits) and by insulin-stimulated autophosphorylation (specifically labeling beta-subunits). The results show that the insulin receptor exists under different free and disulfide-linked combinations of alpha and beta subunits. Moreover, the insulin receptor is closely associated to class I antigens of the major histocompatibility complex to form a high molecular weight multi-molecular membrane complex.

Adenosine Triphosphate↗
PubMedDate not supplied

Structure-function relationships of des-(B26-B30)-insulin.

In order to study the role of the amino acid in position B25 and its environment in shortened insulins, a series of analogues was prepared with the following modifications: 1, Stepwise shortening of the B-chain including replacements of TyrB26 and ThrB27 by glycine; 2, substitutions at the carboxamide nitrogen of des-(B26-B30)-insulin-B25-amide by apolar, polar or charged residues of various chain lengths; 3, replacement of PheB25 by asparagine-amide, phenylalaninol or a series of alkyl and aralkyl residues. Trypsin-catalyzed semisyntheses were performed with Boc-protected or unprotected des-octapeptide-(B23-B30)-insulin and synthetic peptides. Relative receptor binding and in vitro bioactivity of [AsnB25]-des-(B26-B30)-insulin-B25-amide was 227 and 292% (on insulin), other activities ranged between 1 and ca. 200%. We make the following conclusions. An L-amino acid is essential in position B25. The B25-carbonyl and NH groups favour high binding and "superpotency", but are not indispensible for receptor contacts. For high affinity receptor interaction, the planarity at the C gamma-atom and the distance of B25-side-chain branching in position B25 are important, but an aromatic ring is not necessary.

Adipocytes↗
PubMedDate not supplied

[Artificial H-2 dependent carrier determinants of the insulin molecule].

The known tertiary structure of insulin allows the study of carrierdeterminants of insulin: their nature, their distance to antigenic determinants and their H-2 dependance. We examined the influence of "foreign " amino acids of insulins from two different species and the influence of chemically coupled new amino acids at the B-chain of insulin in congenic resistant mice. Three strains were immunized with bovine insulin and three derivatives: LeuB-insulin, LysB-insulin and GluB-insulin. H-2d mice were high responders to insulin and all derivatives, while H-2k mice showed no detectable antibodies. The H-2b strain had an intermediate antibody response to bovine insulin. LeuB-insulin, LysB-insulin and GluB-insulin produced similar titers as unmodified insulin in H-2d mice. In H-2b mice, GluB-insulin produced significantly more antibodies than did all other insulins tested with antibody specificities directed against A8-A10. Therefore Glu at position B0 acts as a carrierdeterminant and A8-A10 as antigenic determinant at the dose utilised in H-2b mice. The distance between both determinants is about 15-20 A, allowing therefore the cooperation of T and B cell.

Animals↗