Mattern R H, Amino Y, Benedetti E, Goodman M
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, USA.
J Pept Res. 1997 Oct;50(4):286-99. doi: 10.1111/j.1399-3011.1997.tb01470.x.
Four potent sweet-tasting molecules, N-(3,3-dimethylbutyl)-L-aspartyl-L-phenylalanine methylester 1 (7000 times more potent than sucrose), N-(3,3-dimethylbutyl)-L-aspartyl-D-valine (S)-alpha-ethylbenzylamide 2 (3000 time more potent than sucrose), L-aspartyl-D-valine (R)-alpha-methoxymethylbenzylamide 3 (1350 times more potent than sucrose and L-aspartyl-(1R,2S,4S)-1-methyl-2-hydroxy-4-phenylhexylamide 4 (2500 times more potent than sucrose) were studied by 1H NMR and computer simulations. These flexible molecules adopt multiple conformations in solution. The "L-shaped" structure, which we believe to be responsible for sweet taste is accessible to all four compounds in solution. Extended conformations with the AH and B-containing moieties in the +y-axis and the hydrophobic group X pointing in the y-axis have also been observed for all four sweeteners. For compounds 1 and 3, the solid-state conformations were determined by X-ray diffraction studies. These results demonstrate that compounds 1 and 3 adopt an "L-shaped" structure even in the crystalline state. The extraordinary potency of the N-alkylated compound 1 compared with the unsubstituted Asp-Phe-OMe may be explained by the effect of a second hydrophobic binding domain in addition to interactions arising from the "L-shaped" structure.
通过¹H NMR和计算机模拟研究了四种强效甜味分子：N-(3,3-二甲基丁基)-L-天冬氨酰-L-苯丙氨酸甲酯1（甜度比蔗糖高7000倍）、N-(3,3-二甲基丁基)-L-天冬氨酰-D-缬氨酸(S)-α-乙基苄基酰胺2（甜度比蔗糖高3000倍）、L-天冬氨酰-D-缬氨酸(R)-α-甲氧基甲基苄基酰胺3（甜度比蔗糖高1350倍）和L-天冬氨酰-(1R,2S,4S)-1-甲基-2-羟基-4-苯基己酰胺4（甜度比蔗糖高2500倍）。这些柔性分子在溶液中呈现多种构象。我们认为负责产生甜味的“L形”结构在溶液中对所有四种化合物都是可及的。对于所有四种甜味剂，还观察到了扩展构象，其中含AH和B的部分在+y轴上，疏水基团X指向y轴。对于化合物1和3，通过X射线衍射研究确定了固态构象。这些结果表明，化合物1和3即使在结晶状态下也采用“L形”结构。与未取代的天冬氨酰苯丙氨酸甲酯相比，N-烷基化化合物1的非凡甜度可能是由第二个疏水结合域的作用以及“L形”结构产生的相互作用共同解释的。
