Cross-linked [DAlaA1]Insulins. Evidence for a change in the conformation of the insulin monomer at its receptor.
[(Boc-DAla)2A1,B1]Insulin was produced by reaction of insulin with phenylisothiocyanate, protection of the B29-epsilon-amino function with the Msc residue, Edman degradation, reaction of A2 and B2 with Boc-DAla-ONSu, and removal of the Msc group. This derivative was used to prepare [DAla2A1,B1]insulin, a B29-B29' dimer, and N alpha A1, N epsilon B29-diaminosuberoyl-[DAla2 A1,B1]-insulin. These derivatives had lipogenic potencies similar to those already reported for analogous derivatives of native insulin (87%, 2.8%, and 8.7% respectively). This suggests that the low activities observed for A1-B29 cross-linked insulins is not due to perturbation of the N-terminus of the A chain. It is argued that the hindrance of a slight conformational adjustment involving the C-terminus of the B chain by the cross-link is a more likely explanation.
D000818:Animals; D001681:Biological Assay; D003432:Cross-Linking Reagents; D007328:Insulin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D011487:Protein Conformation; D011972:Receptor, Insulin / Q000378:metabolism*
D003432:Cross-Linking Reagents; D007328:Insulin; C017008:insulin, Ala(A1)-; D011972:Receptor, Insulin