[On the partial reduction of insulin].
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
H G Gattner
Publications and source records attributed to H G Gattner.
Presentation of insulin and insulin A chain peptides to mouse T cells: involvement of cysteine residues.
The requirements for insulin presentation and recognition by A alpha b A beta b- and A alpha b A beta k-restricted mouse T cells were studied using a variety of derivatives of the insulin A chain. It was found that A chain peptides with irreversibly blocked Cys residues are non-stimulatory for the T cells. This suggests that at least one of the Cys residues is essential for recognition. On the other hand, all A chain peptides containing Cys residues modified in a way reversible by reaction with thiols are stimulatory yet differ in antigenic potency. All these A chain derivatives including a 14 amino acid fragment require uptake by antigen presenting cells (APC) for efficient presentation. Differences in stimulatory potency between the A chain peptides derived from the same insulin appear to be mainly due to the efficiency of uptake and/or processing by APC. Based on these findings we propose that processing in the case of insulin and its A chain derivatives involves the reductive deblocking of Cys residues or the rearrangement of disulfide bonds apart from a possible proteolytic cleavage. The same may apply to other proteins if Cys residues in the presented peptides are important for the interaction with Ia or the T cell receptor.
Animals↗
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↗