Date on Master's Thesis/Doctoral Dissertation


Document Type

Master's Thesis

Degree Name



Oral Biology

Committee Chair

Demuth, Donald R.


Periodontitis--Treatment; Peptides--Therapeutic use


Periodontitis and its systemic sequelae remain a major public health problem and developing a cost-efficient therapy will benefit healthcare worldwide. Adherence of Porphyromonas gingivalis to Streptococcus gordonii facilitates colonization of the oral cavity by P. gingivalis and contributes to development of periodontal disease. It has been demonstrated that synthetic peptides (BAR-peptides) inhibit this interaction and the formation of P. gingivalis biofilms. However, peptides are susceptible to proteolytic degradation thereby precluding their use as therapeutic agents. Consequently, rationallydesigned small-molecule peptidomimetics of BAR will potently inhibit P. gingivalis adherence to S. gordonii and represent viable therapeutic compounds. In terms of inhibitor design, a small molecule "click" strategy was employed whereby the azidebearing partner constitutes a trisubstituted oxazole framework and the terminal acetylene partner constitutes a 5-ethynylmethylene-l ,3-diaminotriazine framework. The design, synthesis and chemistry of the coupling partners in both the acetylenic and azido series have been developed, and the use of these compounds as therapeutic agents is discussed.