Maguire P A, Loew G H
Molecular Research Institute, Palo Alto, CA 94304, USA.
Eur J Pharmacol. 1996 Dec 30;318(2-3):505-9. doi: 10.1016/s0014-2999(96)00894-1.
The goal of this study was to determine the relative contribution of entropy and enthalpy to the free energies of binding to recombinant mouse delta-opioid receptors for the peptide agonist, DPDPE ([D-Pen2,D-Pen5]enkephalin), the peptide antagonist, TIPP(psi) (Tyr-Tic(psi)[CH2NH]Phe-Phe-OH), the nonpeptide agonist, SNC80 ((+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl )-3-methoxybenzyl]-N,N-diethylbenzamide), and the nonpeptide antagonist, naltrindole. Competitive binding studies were carried out using [3H]naltrindole at 0 degrees C, 12 degrees C, 25 degrees C and 37 degrees C, the affinities calculated and van't Hoff plots constructed for each ligand. The temperature dependence of binding and van't Hoff plots indicated that the entropy contribution is the major component of the free energy, for all four ligands, independent of its activity or chemical nature.
本研究的目的是确定熵和焓对肽激动剂DPDPE（[D-青霉胺2，D-青霉胺5]脑啡肽）、肽拮抗剂TIPP(ψ)（酪氨酸- Tic(ψ)[CH2NH]苯丙氨酸-苯丙氨酸-OH）、非肽激动剂SNC80（(+)-4-[(αR)-α-((2S,5R)-4-烯丙基-2,5-二甲基-1-哌嗪基)-3-甲氧基苄基]-N,N-二乙基苯甲酰胺）和非肽拮抗剂纳曲吲哚与重组小鼠δ-阿片受体结合自由能的相对贡献。使用[3H]纳曲吲哚在0℃、12℃、25℃和37℃下进行竞争性结合研究，计算每种配体的亲和力并构建范特霍夫图。结合的温度依赖性和范特霍夫图表明，对于所有四种配体，熵贡献是自由能的主要组成部分，与其活性或化学性质无关。
