Sardinia M F, Hanesworth J M, Krishnan F, Harding J W
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman 99164-6520.
Peptides. 1994;15(8):1399-406. doi: 10.1016/0196-9781(94)90115-5.
The effect of structural changes in the N-terminal amino acid of AIV, with respect to AT4 receptor binding, was examined by competition with [125I]AIV in bovine adrenal membranes. Analogues with modifications of the first residue alpha-amino group possessed lower affinities than the primary amine-containing parent compound. Peptides with a residue 1 alpha-carbon in the D conformation exhibited poor affinity for the AT4 receptor. Modifications of the residue 1 R-group demonstrate that a straight chain aliphatic moiety containing four carbons is optimal for receptor-ligand binding, as evidenced by the extremely high affinity of [Nle1]AIV (Ki = 3.59 +/- 0.51 pM). Replacement of the 1-2 peptide bond of AIV with the methylene bond isostere psi (CH2-NH), increased the Ki approximately fivefold, indicating that the peptide bond may be replaced while maintaining relatively high-affinity receptor binding.
通过在牛肾上腺膜中与[125I]AIV竞争，研究了禽流感病毒（AIV）N端氨基酸结构变化对AT4受体结合的影响。第一个残基α-氨基发生修饰的类似物，其亲和力低于含伯胺的母体化合物。第1位残基α-碳呈D构象的肽对AT4受体的亲和力较差。第1位残基R基团的修饰表明，含四个碳的直链脂肪族部分对受体-配体结合最为理想，[Nle1]AIV的极高亲和力（Ki = 3.59 +/- 0.51 pM）证明了这一点。用亚甲基键类似物psi（CH2-NH）取代AIV的1-2肽键，使Ki增加了约五倍，这表明在保持相对高亲和力受体结合的同时，肽键可以被取代。
