Studies on the total synthesis of an A7,B7-dicarbainsulin. III. Assembly of segments and generation of biological activity.
As a further contribution to the synthesis of an insulin analogue with a stable A7-B7 interchain bond, the synthesis of A(8-21) by solution methods, and of B(9-25) as well as [7-(2,7-diaminosuberic acid)]B(1-8) by solid phase methods is described. In the latter compound, the amino group of the diaminosuberic acid residue was acylated with A(1-6), and the resulting "U-peptide" sequentially elongated with the C-terminal A- and finally B-chain sequences. The conversion of the product into the disulfide moiety gave a mixture which could not be resolved by currently available methods. However, the low biological activity of the crude product indicates that the A7-B7 disulfide bond is not crucially important for the activity of insulin.
Videnov
G
G
Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia.
Büttner
K
K
Casaretto
M
M
Föhles
J
J
Gattner
H G
HG
Stoev
S
S
Brandenburg
D
D
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D008066:Lipolysis; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D007328:Insulin; D013438:Sulfhydryl Compounds; C062660:insulin, dicarbain(A7,B7)-; D014443:Tyrosine; D011972:Receptor, Insulin