Synthesis and dopamine receptor modulating activity of 3-substituted γ-lactam peptidomimetics of L-prolyl-L-leucyl-glycinamide
Synthesis and dopamine receptor modulating activity of 3-substituted γ-lactam peptidomimetics of L-prolyl-L-leucyl-glycinamide
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DOI：
10.1021/jm020441o
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发表时间：
2003-02-27
影响因子：
7.3
通讯作者：
Johnson, RL
中科院分区：
文献类型：
--
作者：
Dolbeare, K;Pontoriero, GF;Johnson, RL
γ-内酰胺Pro-Leu-Gly-NH 2（PLG）的肽模拟物2在3-位被异丁基、丁基和苄基部分取代，分别得到PLG肽模拟物3-5。合成这些化合物以测试将疏水部分连接到内酰胺环以模拟PLG的亮氨酰基残基的异丁基侧链将增加此类肽模拟物的多巴胺受体调节活性的假设。测试这些肽模拟物增强[H-3]-N-丙基去甲阿朴吗啡与从牛纹状体膜分离的多巴胺受体结合的能力。3位取代基的取代效果顺序为苄基>正丁基>异丁基> H。
gamma-Lactam. peptidomimetic 2 of Pro-Leu-Gly-NH2 (PLG) was substituted at the 3-position with isobutyl, butyl, and benzyl moieties to give the PLG peptidomimetics 3-5, respectively. These compounds were synthesized to test the hypothesis that attaching a hydrophobic moiety to the lactam ring to mimic the isobutyl side chain of the leucyl residue of PLG would increase the dopamine receptor modulating activity of such peptidomimetics. These peptidomimetics were tested for their ability to enhance the binding of [H-3]-N-propylnorapomorphine to dopamine receptors isolated from bovine striatal membranes. The rank order of effectiveness of the 3-substituent was benzyl > n-butyl > isobutyl > H.