title: Antiadhesion as a functional concept for prevention of pathogens: N-Phenylpropenoyl-L-amino acid amides as inhibitors of the Helicobacter pylori BabA outer membrane protein.
abstract: METHODS
  Besides flavan-3-ols, a family of N-phenylpropenoyl-L-amino acids (NPAs) has been recently identified as polyphenol/amino acid conjugates in the seeds of Theobroma cacao as well as in a variety of herbal drugs. NPAs were shown to exhibit antiadhesive activities against Helicobacter pylori.
  
  
  RESULTS
  For structure/activity relationship 24 homologous NPAs (2 mM) were investigated in a flow cytometric assay on potential antiadhesive effects against H. pylori adhesion to human gastric AGS cells. Dihydroxylation of the aromatic molecule part was shown to be necessary for activity; methoxylation decreases activity. High polarity of the amino acid is a prerequisite for activity. The model compound N-(E)-caffeoyl-L-glutamic acid 11 exerted a concentration-dependent inhibition of bacterial adhesion with saturation at 30% inhibition level. The antiadhesive effect was additionally confirmed by in situ adhesion assay on intact human gastric tissue. NPAs exhibited no cytotoxicity. Using immobilized ligands interaction 11 with bacterial adhesin BabA was demonstrated. RT-PCR indicated that the inhibition of BabA is not correlated with subsequent feed back regulations to express more adhesins or virulence factors (vacA, cagA, cagL, cagα, fucT, ureI, ureA, OMPs). The interaction of bacterial adhesins with the respective ligands does not automatically lead to a subsequent signal transduction towards induction of virulence processes.
  
  
  CONCLUSIONS
  The nutritional use of NPA-containing food may justify a positive antiadhesive effect against the recurrence of H. pylori infections.
authors.affiliation: University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Niehues
authors.forename: Timo
authors.initials: T
authors.lastname: Stark
authors.forename: Daniela
authors.initials: D
authors.lastname: Keller
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Hensel
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D018829:Adhesins, Bacterial / Q000187:drug effects*; D000577:Amides / Q000494:pharmacology; D000596:Amino Acids / Q000737:chemistry* / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000235:genetics; D001422:Bacterial Adhesion / Q000187:drug effects*; D001425:Bacterial Outer Membrane Proteins / Q000187:drug effects; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005434:Flow Cytometry; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005971:Glutamates / Q000737:chemistry / Q000494:pharmacology; D016480:Helicobacter pylori / Q000187:drug effects / Q000472:pathogenicity*; D006386:Hemagglutination Tests; D006801:Humans; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000473:pathology; D013329:Structure-Activity Relationship; D037521:Virulence Factors / Q000235:genetics
chemical_list: D018829:Adhesins, Bacterial; D000577:Amides; D000596:Amino Acids; D000942:Antigens, Bacterial; C400429:BabA protein, Helicobacter pylori; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002109:Caffeic Acids; D003603:Cytotoxins; D005971:Glutamates; D026901:Membrane Transport Proteins; C561920:N-caffeoylglutamic acid; C114527:UreI protein, Helicobacter pylori; C074689:VacA protein, Helicobacter pylori; D037521:Virulence Factors; C080866:cagA protein, Helicobacter pylori