Biomedical subjects
E Haslam
Publications and source records attributed to E Haslam.
Multiple interactions between polyphenols and a salivary proline-rich protein repeat result in complexation and precipitation.
Polyphenols (tannins) in the diet not only precipitate oral proteins, producing an astringent sensation, but also interact with dietary proteins and digestive enzymes in the gut, resulting in a variety of antinutritive and toxic effects. Salivary proline-rich proteins (PRPs), which are secreted into the oral cavity, form complexes with and precipitate dietary polyphenols, and thus, they constitute the primary mammalian defense directed against ingested tannins. In order to characterize the interaction, NMR studies were performed which involved titrating a series of polyphenols into a synthetic 19-residue PRP fragment. The results show that the predominant mode of association is a hydrophobic stacking of the polyphenol ring against the pro-S face of proline and that the first proline residue of a Pro-Pro sequence is a particularly favored binding site. Measurement of dissociation constants indicates that the larger and more complex polyphenols interact more strongly with the PRP fragment; the order of binding affinity was determined as procyanidin dimer B-2 > pentagalloylglucose > trigalloylglucose >> proanthocyanidin monomer (-)-epicatechin approximately propyl gallate. Smaller polyphenols can bind with one phenolic ring stacked against each proline residue, whereas larger polyphenols occupy two or three consecutive prolines. The more complex polyphenols interact with the PRP fragment in a multidentate fashion; moreover, they self-associate or stack when bound. Thus, a model is proposed in which multiple polyphenol/polyphenol and polyphenol/PRP interactions act cooperatively to achieve precipitation.
Tannin interactions with a full-length human salivary proline-rich protein display a stronger affinity than with single proline-rich repeats.
The protein IB5 has been purified from human parotid saliva. This protein contains several repeats of a short proline-rich sequence. Dissociation constants have been measured at several discrete binding sites using 1H-NMR for the hydrolysable tannins (polyphenols) beta-1,3,6-tri-O-galloyl-D-glucopyranose, beta-1,2,4,6-tetra-O-galloyl-D-glucopyranose and beta-1,2,3,4,6-penta-O-galloyl-D-glucopyranose and the condensed proanthocyanidin (--)-epicatechin. The dissociation constants for trigalloyl glucose and pentagalloyl glucose were 15 X 10(-5) and 1.7 X 10(-5) M, respectively, which are 115 and 1660 times stronger than those previously measured under the same conditions for a single repeat of a mouse salivary proline-rich protein. The increase in affinity is ascribed to intramolecular secondary interactions, which are strengthened by the rigidity of the interacting molecules.
Natural polyphenols (vegetable tannins) as drugs: possible modes of action.
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Study of the interaction between salivary proline-rich proteins and a polyphenol by 1H-NMR spectroscopy.
The interaction between salivary proline-rich proteins and plant polyphenols (tannins) in the oral cavity and their subsequent precipitation influences the taste, texture and nutritional value of food; it is thought to be responsible for the astringency of many foods and beverages. To investigate the interaction, two-dimensional 1H-NMR studies have been carried out on the binding of a representative polyphenol, pentagalloyl glucose, to two synthetic peptides (19 and 22 residues in length) that are typical of the repeat sequence of mouse salivary proline-rich protein MP5. Intermolecular nuclear Overhauser effects and chemical shift changes show that the main binding sites on the peptides are proline residues together with the preceding amide bond and amino acid. The interaction is principally a hydrophobic association between a galloyl ring and the pyrrolidine ring face containing the C alpha proton, but secondary hydrogen-bonding effects help to stabilise the complex. Very similar interactions are seen for both peptides. The conformation of the peptides remains extended on binding. The chemical shift changes seen for many of the peptide protons can be fitted to a simple binding curve with dissociation constant of around 40 mM, but some protons show evidence of cooperative binding involving several galloyl groups. Higher concentrations of pentagalloyl glucose lead to a reduced off-rate from the complex and eventual precipitation which implies that precipitation is caused by a kinetic competition between aggregation and dissociation of the complex.
Polyphenols, astringency and proline-rich proteins.
Recent, NMR and precipitation, studies of molecular recognition of proline-rich proteins and peptides by plant polyphenols are described and rationalized. The action of polysaccharides and caseins in the moderation of the astringent response, which is engendered by polyphenols present in foodstuffs and beverages, is described. The possible influence of plant cell wall glycoproteins on the process of lignification is discussed in the light of the observed affinity of phenolic substrates for prolyl residues in protein structures.
Traditional herbal medicines--the role of polyphenols.
The polyphenol composition of some traditional herbal remedies is reviewed. Polyphenols probably act in such remedies by virtue of their astringent action and current views on the molecular basis of this property are outlined and discussed.
Interactions of natural phenols with macromolecules.
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The shikimate pathway. Part V. Chorismic acid and chorismate mutase.
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The shikimate pathway. IV. The stereochemistry of the 3-dehydroquinate dehydratase reaction and observations on 3-dehydroquinate synthetase.
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Polyphenol-protein interactions.
The association of some natural and synthetic polyphenols with beta-glucosidase was examined and some observations on the chemical nature of the complex were made.
The Shikimate pathway. 3. The stereochemical course of the L-phenylalanine ammonia lyase reaction.
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(+)-catechin-3-gallate and a polymeric proanthocyanidin from Bergenia species.
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Phenol biosynthesis in higher plants. Gallic acid.
The biosynthesis of gallic acid in a number of higher plants was investigated by using l-[U-(14)C]phenylalanine, (-)-[G-(14)C]shikimic acid, d-[1-(14)C]glucose and d-[6-(14)C]glucose as tracers. The results are compared with those obtained similarly for caffeic acid and are interpreted in terms of the dehydrogenation of 5-dehydroshikimic acid as a normal route of metabolism for gallic acid.
Microbiological chemistry.
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The oxidation of some pyrogallol and purpurogallin derivatives.
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The esterase and depsidase activities of tannase.
The esterase and depsidase activities of tannase have been examined by kinetic methods. Although the esterase/depsidase ratio of tannase may be varied by cultural methods and isolation procedures, evidence has been obtained to show that tannase, esterase and depsidase are enzymes with low specificities capable of hydrolysing both esters and depsides of gallic acid.