Studies On The Quantitative Structure-pungency Relationship Of Capsaicinoids And The Interaction With Bovine Serum Albumin

The comprehensive understanding of the mechanism of spiciness and its interaction with its receptor has attracted more and more attention in the field of food science and technology.To date,the investigations on the pungency of capsicum plants and capsaicinoids have mainly focused on the following aspects:the the sensory evalution of pungent compounds from food matrices and the mechanistic understanding of pungency from the biological and chemical perspectives and the dynamic pungency evaluation of pungent compounds affected by other tastes and flavor stimuli from food sources.Though there are a great deal of research on the structure and it's activity and property of capsaicinoids.But it cannot meet the requirement of quantitative evaluation of compound spiciness.Understanding the spiciness of capsaicinoids is a challenge due to the complex interaction between capsaicinoids and its receptor.Therefore,it is meaningful to establish the quantitative relationship between the properties of capsaicinoids and their spiciness,which is helpful for us to understand the mechanism of spiciness.In addition,when capsaiciniods are absorbed by our body,it is transported to the blood by the serum protein and then they can make physiological effects to our body.But at present there are few reports about the distribution and transport mechanism of capsaicinoids.Therefore,in this paper,the two-dimensional/three-dimensional quantitative structure-activity relationship(2D/3D-QSPR)models of capsaicinoids and their spiciness were established using the statistical algorithms in Materials Studio and Discovery Studio software respectively.It suggested the quantitative relationship between their structural parameters and the spiciness,which guided the design of spiciness molecules.Meanwhile,with bovine serum protein(BSA)as the model protein,the interaction between capsaicinoids and BSA was studied.The main results of the research are as follows:(1)In this paper,the quantitative structure-spiciness relationship of capsaicinoids were studied.There are four models including linear and quadratic 2D-QSPR models are constructed respectively by using genetic function approximation algorithm.All the models passed the significanoe test of cross-validation,random test,external prediction,Roy'rm2 metrics and Golbraikh-Tropsha standards and other statistical methods.It indicated that all models have strong internal and external prediction ability(r2 = 0.949?0.989,r2cv = 0.860?0.955,r2pred = 0.859?0.904).The results showed that HOMO and other electrostatic parameters,S_ssNH and other hydrogen bond parameters,AlogP and other hydrophobic parameters and Shadow area:ZX plane and other steric parameters were the key structural parameters affecting the spiciness of capsaicinoids.On this basis,this paper adopts partial least square method to establish the 3D-QSAR model between the spiciness of capsaicinoids and the interaction energy between molecules and grid points in electrostatic field and steric field.The optimal model had strong external prediction ability through cross-validation and external prediction(r2 =0.983,r2cv = 0.644,r2pred = 0.904).The results showed that the spiciness could be greatly improved through the addition of the linear chain group or positive charge to the methoxy group which was attached to the benzene ring,and the addition of group with positive charge at the 4-6 substituent group,and the addition of negative or larger group to the 9 methyl group and the hydroxyl group attached to the benzene ring,and the addition of negative or larger group to hydroxyl group which was attached to the benzene ring.Based on the analysis of the above models,62 newly capsaicinoids were designed,and the study showed that the pungency of most of the newly designed capsaicinoids was distributed in the range of 1.0×106 SHU?1.0×107 SHU and most of them had acceptable ADME&T properties which were similiar to known capsaicinoids.(2)The interaction between capsaiciniods and serum proteinThe interaction between capsaicin and Bovine serum albumin(BSA)was studied by combining various spectral methods and molecular docking.The results of steady-state fluorescence spectra showed that capsaicin induced endogenous fluorescence quenching of BSA by forming a ground state complex with BSA.According to van't Hoff's equation,the enthalpy change and entropy change were all less than zero,indicating that the hydrogen bond and van der Waals force between molecules were the main driving forces for the combination of them.The UV-Visible absorption spectrum experiment showed that there was non-radiative energy transfer between capsaicin and BSA.When the molar ratio of capsaicin and BSA was 1:1,the binding distance between capsaicin and the tryptophan residue of BSA was 3.053 nm and the critical distance was 5.315 nm.The results of circular dichroism showed that the presence of capsaicin would change the spatial conformation of BSA,the content of a-helix decreased,and the content of ?-turn and random increased.The microenvironment in the vicinity of tryptophan and tyrosine was changed,and the hydrophobicity increased.The molecular docking showed that capsaicin mainly bound to the hydrophobic cavity of subdomain ?A of BSA,and interacted with the main hydrophobic amino acid residues in the cavity,and forms the hydrogen bond with histidine His241 and alanine Ala290.From the molecular docking diagram of capsaicin and BSA system,it suggested capsaicin interacted with the TRP213 residue of BSA,which was the reason that capsaicin queching the fluorescence of BSA.The results of molecular docking of other capsaicinoids with BSA showed that the number branched-chain methyl of fatty side chain and hydroxyl of capsaicinoids were both structural factors influencing the binding of capsaicin with BSA.Studies on the structure-activity relationship of capsaicin provide a scientific basis for the comprehensive understanding of the relationship between the structure of capsaicinoids and their spiciness.It would lay a foundation for further and systematic research on the mechanism of spiciness.At the same time,the research on the structural factors of capsaicinoids to regulate the spice taste provided theoretical guidance for the development of new capsaicinoids.Through studying the interaction between capsaicin and BSA,it is of great significance to further understand the transport,absorption,distribution,metabolism and pharmacological action of food active ingredients in our body.