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以DOI为原料,合成了一些DHI的类似物。生物活力说明,DHI的B_(23)甘氨酸为含疏水侧链的L-型氨基酸Ala,Val和Phe取代时,所得DHI类似物不表现胰岛素活力。B_(23)以L-型Asn或Ser取代时,出现较弱的胰岛素活力;而以D-型氨基酸Ala,Val取代时,具5—10％的活力(指粗产物活力,下同);D-Phe取代时,具约5％的生物活力;D-Ser取代时,具2％的生物活力。DHI的B_(24)苯丙氨酸残基以Arg,Glu或Ser取代后不表现胰岛素活力。以Tyr或苯甲胺取代时,具2％左右的活力。但DOI-Gly·Gly·Phe具约2％的胰岛素活力,而DOI-Gly·Gly-D-Phe却无活力。此结果说明,B_(24)或B_(25)的一个芳香环是胰岛素活力所必需的。联系胰岛素晶体结构的研究结果,本文还初步讨论了导致上述现象的分子结构的内在原因。
Using DOI as raw material, some analogues of DHI were synthesized. Bioactivities show that DHI analogues do not exhibit insulin activity when the B23 glycine of DHI is substituted with hydrophobic side chains of the L-amino acids Ala, Val and Phe. When B_ (23) was replaced by L-Asn or Ser, weaker insulin activity was found. When D_type amino acids Ala and Val were substituted, the activity of B_ (23) was 5-10% (crude activity, same below) Substitution with D-Phe, with about 5% of the biological activity; D-Ser substitution, with 2% of biological activity. The B_ (24) phenylalanine residue of DHI did not show insulin activity after substitution with Arg, Glu or Ser. Substitution with Tyr or benzylamine, with about 2% activity. However, DOI-Gly · Gly · Phe had about 2% insulin activity, whereas DOI-Gly · Gly-D-Phe had no viability. This result shows that an aromatic ring of B_ (24) or B_ (25) is necessary for insulin activity. In connection with the research results of insulin crystal structure, this paper also initially discussed the underlying causes of the molecular structure leading to the above phenomenon.