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Die Synthese von Insulinfragmenten mit intakter interchenarer Disulfidbrücke A 20 ‐B 19
Author(s) -
Kamber B.
Publication year - 1971
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19710540143
Subject(s) - chemistry , cysteine , residue (chemistry) , peptide , cystine , stereochemistry , hydrochloric acid , disulfide bond , amino acid , peptide synthesis , disproportionation , organic chemistry , enzyme , catalysis , biochemistry
The synthesis of six insulin fragments is described, in which various sequences of the two chains are linked by the disulfide bridge between A 20 and B 19 . The fragments in question are: A 20–21 –B 19–21 , A 20–21 –B 18–21 , A 20–21 –B 17–21 , A 19–21 –B 19–21 , A 16–21 –B 18–21 and A 20–21 –B 12–21 . In order to build up the simpler fragments the disulfide bridge was established by oxidation with iodine of two S‐trityl cysteine peptides in which the carboxyl and amino groups were protected by the t ‐butyl and t ‐butyloxycarbonyl residue. From the mixture obtained the unsymmetrical cystine peptide was separated in all cases from the two symmetrical ones by counter‐current distribution. In the synthesis of the more complex fragments advantageous use was made of smaller unsymmetrical fragments prepared as above but having one amino group protected by the N‐trityl residue. After selective elimination of this group it was possible to lengthen the peptide chain at this position. The free peptides were obtained by removal of the protecting groups with strong acids, in particular concentrated hydrochloric acid. While in this deprotecting step the disulfide bond was stable, conditions are discussed under which disproportionation was observed. None of the six synthetic insulin fragments showed activity in stimulating rat adipose tissue to convert 14 C‐labelled glucose to CO 2 in vitro .