Towards a Molecular Interpretation of Astringency: Synthesis, 3D Structure, Colloidal State, and Human Saliva Protein Recognition of Procyanidins

Abstract

Astringency is a sensation in the mouth used in judging the quality of red wine. The rough, dry, and puckering sensation called astringency is the result of an interaction between tannins and saliva proteins, mainly proline-rich proteins (PRP), which leads to the formation and precipitation of a complex. A dry and rough sensation is then perceived in the mouth. To get an insight into astringency at the molecular level we investigated: (i) An efficient and iterative method for 4–8 procyanidin synthesis, which gives rise to all possible 4–8 procyanidins up to the tetramer with total control of degree of oligomerization and stereochemistry. (ii) The 3D‐structural preferences, which take into account their internal movements, using 2D NMR and molecular modeling. (iii) The self-association process in water or hydroalcoholic solutions using diffusion NMR spectroscopy that gives the active proportion of tannins able to fix proteins. (iv) A comprehensive description of the PRP-procyanidin complex formation to get information about stoichiometry, binding site localization, and affinity constants for different procyanidins. The data collected suggest that the interactions are controlled by both procyanidin conformational and colloidal state preferences. All these results provide new insights into the molecular interpretation of tannin astringency.

procyanidin - proline rich peptide - astringency - NMR - molecular dynamics

References

• 1 Joslyn M A, Goldstein J L. Astringency of fruit and fruit products in relation to phenolic content. Chichester; New York Academic Press 1964
• 2 Bate-Smith E C. Astringency in foods.  Foods. 1954;  23 124-134
• 3 Gawel R, Iland P G, Francis I L. Characterizing the astringency of red wine: a case study.  Food Qual Prefer. 2001;  12 83-94
• 4 Bate-Smith E C, Swain T. Flavonoid compounds. Florkin M, Mason HS Comparative biochemistry, Vol. 3. New York; Academic Press 1962: 75-809
• 5 Ribéreau-Gayon P. Plant phenolics. Edinburgh; Oliver and Boyd 1972
• 6 Tarascou I, Barathieu K, Andre Y, Pianet I, Dufourc E J, Fouquet E. An improved synthesis of procyanidin dimers: Regio- and stereocontrol of the interflavan bond.  Eur J Org Chem. 2006;  23 5367-5377
• 7 Tarascou I, Barathieu K, Simon C, Ducasse M A, Andre Y, Fouquet E, Dufourc E J, de Freitas V, Laguerre M, Pianet I. A 3D structural and conformational study of procyanidin dimers in water and hydro-alcoholic media as viewed by NMR and molecular modeling.  Magn Reson Chem. 2006;  44 868-880
• 8 Tarascou I, Ducasse M A, Dufourc E J, Moskau D, Fouquet E, Laguerre M, Pianet I. Structural and conformational analysis of two procyanidin trimers.  Magn Reson Chem. 2007;  45 157-166
• 9 Pianet I, Andre Y, Ducasse M A, Tarascou I, Lartigue J C, Pinaud N, Fouquet E, Dufourc E J, Laguerre M. Modeling procyanidin self-association processes and understanding their micellar organization: a study by diffusion NMR and molecular mechanics.  Langmuir. 2008;  24 11027-11035
• 10 Hagerman A E, Butler L G. The specificity of proanthocyanidin-protein interactions.  J Biol Chem. 1981;  256 4494-4497
• 11 Cala O, Pinaud N, Simon C, Fouquet E, Laguerre M, Dufourc E J, Pianet I. NMR and Molecular Modeling of wine tannins binding to saliva proteins: revisiting astringency from molecular and colloidal prospect.  FASEB J. 2010;  24 4281-4290
• 12 Simon C, Pianet I, Dufourc E J. Synthesis and circular dichroism study of the human salivary proline-rich protein IB7.  J Pept Sci. 2003;  9 125-131
• 13 Carteau D, Pianet I, Brunerie P, Guillemat B, Bassani D M. Probing the initial events in the spontaneous emulsification of trans-anethole using dynamic NMR spectroscopy.  Langmuir. 2007;  23 3561-3565
• 14 Baxter N J, Williamson M P, Lilley T H, Haslam E. Stacking interactions between caffeine and methyl gallate.  J Chem Soc Faraday Trans. 1996;  92 231-234
• 15 Charlton A J, Baxter N J, Lilley T H, Haslam E, McDonald C J, Williamson M P. Tannin interactions with a full-length human salivary proline-rich protein display a stronger affinity than with single proline-rich repeats.  FEBS Lett. 1996;  382 289-292
• 16 Tückmantel W, Kozikowski A P, Romancsyk L J. Studies in polyphenol chemistry and bioactivity. 1. Preparation of building blocks from (+)-catechin. Procyanidin formation. Synthesis of the cancer cell growth inhibitor, 3-O-galloyl-(2R,3R)-epicatechin-4,8-[3-O-galloyl-(2R,3R)-epicatechin].  J Am Chem Soc. 1999;  121 12073-12081
• 17 Saito A, Tanaka A, Nakajima N, Ubukata M. Efficient stereoselective synthesis of proanthocyanidin trimers with TMSOTf-catalyzed intermolecular condensation.  SynLett. 2004;  1069-1073
• 18 Steynberg J P, Brandt E V, Ferreira D, Helfer C A, Mattice W L, Gornik D, Hemingway R W. Conformations of procyanidins. Press P Plant polyphenols. New York; R. W. Hemingway and P. E. Laks 1992
• 19 Hatano T, Hemingway R W. Conformational isomerism of phenolic procyanidins: preferred conformations in organic solvents and water.  J Chem Soc [Perkin II]. 1997;  1035-1043
• 20 Price W S. Pulsed-Field gradient nuclear magnetic resonance as a tool for studying translational diffusion: Part 1. Basic theory.  Concepts Magn Reson. 1997;  9 299-336
• 21 Boisselier E, Ornelas C, Pianet I, Aranzaes J R, Astruc D. Four generations of water soluble dendrimers with 9 to 243 benzoate T ethers: synthesis and dendritic effects on their ion paring with acetyl choline, benzyltriethylammonium and dopamine in water.  Chem Eur J. 2008;  14 5577-5587
• 22 Duluard S, Grondin J, Bruneel J L, Pianet I, Grelard A, Campet G, Delville M H, Lassegues J C. Lithium solvation and diffusion in the 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imid ionic liquid.  J Raman Spectrosc. 2008;  39 627-632
• 23 Bennick A. Structural and genetic aspects of proline-rich proteins.  J Dental Res. 1987;  66 457-461
• 24 Charlton A J, Baxter N J, Khan M L, Moir A J G, Haslam E, Davies A P, Williamson M P. Polyphenol/peptide binding precipitation.  J Agric Food Chem. 2002;  50 1593-1601