Porphyromonas gingivalis is a periodontal pathogen that initially colonizes the oral cavity by adhering to S. gordonii via interaction of the minor fimbrial antigen Mfa1 with a specific motif of the streptococcal SspB protein designated BAR. Synthetic peptides representing BAR function are potent inhibitors of P. gingivalis adherence/biofilm formation, but are costly to synthesize and are susceptible to proteolytic cleavage. Thus rationally-designed small molecule peptidomimetics of BAR that inhibit P. gingivalis adherence to S. gordonii may represent potential therapy. A small-molecule click chemistry strategy was used whereby the azide-bearing and acetylenic partners constitute trisubstituted oxazole and diaminotrazine frameworks respectively. Eight azide-bearing compounds were synthesized as mimics of the NITVK motif of BAR. Two compounds partially inhibited planktonic growth of P. gingivalis and three of the compounds were found active at varying levels in inhibition of adherence to streptococci. The synthesis of the heterocyclic click partners and the evaluation of their inhibitory efficacy will be presented.

Synthesis and evaluation of peptidomimetic inhibitors of <i>Porphyromonas gingivalis</i> biofilm formation

245th National Meeting (2013)

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Synthesis and evaluation of peptidomimetic inhibitors of Porphyromonas gingivalis biofilm formation