Abstract:

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=^-O₂C(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-CR¹R²R³ where R³>R²>R¹ 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 C₈ to C₁₀acyl group. If one supposes that the size instead of the atomic number of substituentsR¹R²R³ 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 A₂^c ofthem in series connection G-A₁^c-A₂^c must be of a "topo"-L enantiomer. For a dipeptideG-A^c, the width R¹-C-R² of A^c must be≤(CH₂)₄;for a tripeptide G-A₁^c-A₂^c, that ofA₂^c must be≤(CH₂)₅. The polar, steric and hydrophobic effects of substituents on R, R²and R³ have understandable influences, inter alia, on the stability as well as sweetnessintensity of these concerned sweetencrs.

Key words: glucophore, auxogluc, C-9 rule, "topo"configuration