Rovero P, Pestellini V, Patacchini R, Giuliani S, Maggi C A, Meli A, Giachetti A
Chemistry Department, A. Menarini Pharmaceuticals, Firenze, Italy.
Peptides. 1990 May-Jun;11(3):619-20. doi: 10.1016/0196-9781(90)90067-f.
By introducing D-Trp in position 6 and 8 along with pyroglutamic acid (Pyr) in position 4 or Nle in position 10 of NKA(4-10) we have obtained selective although weak NK-2 tachykinin receptor antagonists. Similar substitutions, previously reported on the sequence of SP, gave rise to nonselective antagonists presumably for the limited selectivity of the agonist used as template. Further modifications like the addition of a third D-Trp in position 9 gave rise to more potent but less selective antagonists, thus showing that each amino acid substitution can dramatically affect selectivity.
通过在NKA(4 - 10)的第6和8位引入D - 色氨酸，同时在第4位引入焦谷氨酸(Pyr)或在第10位引入正亮氨酸(Nle)，我们获得了选择性较弱的NK - 2速激肽受体拮抗剂。先前在速激肽(SP)序列上报道的类似取代产生了非选择性拮抗剂，可能是因为用作模板的激动剂选择性有限。进一步的修饰，如在第9位添加第三个D - 色氨酸，产生了更强效但选择性更低的拮抗剂，从而表明每个氨基酸取代都能显著影响选择性。
