Preliminary crystallographic studies on two insulin analogues which retain high biological activities after alterations in A chain

Using Fmoc solid phase synthesis and site-directed gene mutagenesis, two insulin analogues, [A13-14GABA, A21Ala] porcine insulin and [A3Thr] human insulin, have been prepared respectively, which retain high biological activities. The results show that non-coded yamino butyric acid (GABA) could replace the dipeptide, Leu-Tyr, in A13-A14 of insulin and that the hydrophilic Thr could substitute Val in A3 of insulin which is highly conservative and included in the receptor binding site. The crystal culture and preliminary crystallographic studies by X-ray diffraction on these two insulin analogues are reported.