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New synthesis of somatostatin according to the S ‐ tert ‐butylthiocysteine procedure
Author(s) -
Moroder L.,
Gemeiner M.,
Goehring W.,
Jaeger E.,
Thamm P.,
Wünsch E.
Publication year - 1981
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.1981.360200103
Subject(s) - chemistry , thiol , cysteine , somatostatin , disulfide bond , peptide , cleavage (geology) , peptide synthesis , protecting group , side chain , combinatorial chemistry , stereochemistry , condensation , organic chemistry , biochemistry , polymer , alkyl , thermodynamics , geotechnical engineering , physics , neuroscience , fracture (geology) , engineering , biology , enzyme
To exemplify the usefulness of the S ‐ tert ‐butylthio group for a reversible blocking of the cysteine thiol function in peptide synthesis, fully protected dihydrosomatostatin was prepared by the fragment‐condensation procedure. The experimental results confirm the excellent stability of the asymmetric disulfide under the normal conditions of peptide synthesis and prove that the selective, acid‐catalyzed nucleophil removal—as well as by mercaptans—of the 2‐nitrophenylsulfenyl group proceeds smoothly in the presence of this thiol protection. Thus, the strategy of overall acid‐labile side‐chain protection in combination with the N α ‐2‐nitrophenylsulfenyl group for the chain‐elongation steps can be successfully applied to the synthesis of cysteine‐containing peptides using their S ‐ tert ‐butylthio derivatives. Removal of the acid‐labile groups, followed by reductive cleavage of the asymmetric disulfides and successive air oxidation, allowed a clean conversion of protected dihydrosomatostatin into somatostatin at a high degree of purity and in good yields.