Marastoni M, Guerrini R, Balboni G, Salvadori S, Fantin G, Fogagnolo M, Lazarus L H, Tomatis R
Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, Italy.
Arzneimittelforschung. 1999 Jan;49(1):6-12. doi: 10.1055/s-0031-1300350.
The solid phase synthesis, based on the Fmoc chemical protocol, was used to prepare ten deltorphin C (Del-C; H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) analogues containing cis- and trans- 2 or 3- or 4- aminocyclohexanecarboxylic acid (ACCA) residues at position 2. ACCA-peptides showed high resistance to degradation by plasma or brain enzymes, negligible affinity for the kappa-binding site and modest delta- and/or mu-receptor affinities. Both [cis-3-ACCA2]Del-C analogues and one trans isomer are the only deltorphin analogues of this series exhibiting an appreciable delta-affinity and selectivity. These data suggest that the presence of a conformationally constrained ACCA residue in position 2 of the "message" sequence of deltorphin C is slightly tolerated.
基于Fmoc化学方案的固相合成法被用于制备10种德尔托啡肽C（Del-C；H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2）类似物，这些类似物在第2位含有顺式和反式2-、3-或4-氨基环己烷羧酸（ACCA）残基。ACCA肽对血浆或脑酶的降解具有高度抗性，对κ结合位点的亲和力可忽略不计，对δ和/或μ受体的亲和力适中。两种[顺式-3-ACCA2]Del-C类似物和一种反式异构体是该系列中仅有的表现出明显δ亲和力和选择性的德尔托啡肽类似物。这些数据表明，德尔托啡肽C“信息”序列第2位存在构象受限的ACCA残基的情况在一定程度上是可接受的。
