二肽和三肽甜味剂的结构性能关系

STRUCTURE-ACTIVITY RELATIONSHIPS OF DI-AND TRIPEPTIDE SWEETENERS

本文用作者(1980)提出的多点接触U-型诱导适应甜苦味受体模型说明与Asparta-me类似的二肽三肽甜味剂中结构与性能相互关系。其中生甜基(Glucophore)G=^-O_2C(CH_2)_(0-1)·CHNH_2R^+,R=H;助味基(Auxogluc)A^N=R,R为N-端酰胺基;C-端助味基A^C=CONHC·R^1R^2R^3,此处R^3>R^2>R^1。A^N和A^C的主干链均以其能达到味受体膜的外层中部C-9位时化合物最甜。G的定味位置和方向不同,A^N和A^C主干链可到达的膜层深浅也将不同,然而总以能到达受体膜的C-9位时才能产生最强微扰。故最有利的助味基常以其约相当于一脂肪酸酰基C_9的链长为最好,且过犹不及。若以不对称碳原子上取代基R^1R^2R^3的体积大小(而不是以原子序数大小)作我们称之为“拓朴”构型的准则,则并联三肽A^N-G-A_2~C的三个氨基酸都必需是“拓朴”-D-型才能产生高甜度。而串联三肽G-A_1~C-A_2~C中仅需A_2~C是“拓朴”-L-型。二肽G-A^C中A^C的主干链宽度R^1-C-R^2以≤(CH_2)_4为度;三肽G-A_1~C-A_2~C中A_2~C宽度以≤(CH_2)_5为度。除其他指标外,R,R_2和R_3本身或其取代基所具有极性效应、空间效应,疏水效应对这些甜味剂所产生的甜强度及稳定性的影响都是容易理解的。

A U-shaped induced-fitting model of sweet-bitter receptor with multiple point attach-ment was proposed by the author in 1980. In this paper it is employed to illustrate thestructure-activity relationships of di- and tripeptide sweeteners analogous to Aspartame.The glucophore is taken to be G=^-O_2C(CH-2)_(0-1) CHNH-2^+R when R=H, the auxogluc onthe N-end to be A^N=R when R=any acyl group and that on the C-end to be A^c=CONH-CR^1R^2R^3 where R^3>R^2>R^1 in size. The main chains of both A^N and A^c will attain amaximal sweetness, if either or both can reach the C-9 position of the top layer of thereceptor membrane. However, the depth where the main chain of A^N or A^c can reach de-pends on the orientation and position where G is ancholed on the sulface. Nevertheless, itwill cause the highest perturbation shuold it reach this C-9 position. Thus the optimalchainlength of an auxogluc is often equivalent to no more or less than that of a C_8 to C_(10)acyl group. If one supposes that the size instead of the atomic number of substituentsR^1R^2R^3 on the dissymmetric a-carbon atom be adopted as the standard for what we call'topo' configuration, then the three amino acids in paralle connection A^N-G-A^c must allbe of a 'topo'-D-configuration to have a high sweetness intensity whiie only an A_2~c ofthem in series connection G-A_1~c-A_2~c must be of a 'topo'-L enantiomer. For a dipeptideG-A^c, the width R^1-C-R^2 of A^c must be≤(CH_2)_4;for a tripeptide G-A_1~c-A_2~c, that ofA_2~c must be≤(CH_2)_5. The polar, steric and hydrophobic effects of substituents on R, R^2and R^3 have understandable influences, inter alia, on the stability as well as sweetnessintensity of these concerned sweetencrs.