In 2001, the ACS Orlando Section established the Avogadro Award to be presented to an outstanding senior project at the State Science and Engineering Fair. Other Sections in Florida were encouraged to support the award, and it is presented yearly as a joint effort.
The 2026 award winner is Nicholas R. Stan (pictured right), a student at Alexander W. Dreyfoos School of the Arts in West Palm Beach. Nicholas’ project was entitled “Enhancing the Oncotoxic Effects of Mitochondrial-targeting D-(KLAKLAK)2 Peptide by Improving Cell Membrane Permeability via Chemical Conjugation with Imidazopyidinium.” The judges in the senior chemistry section unanimously chose this project because of its strong chemistry content and the obvious knowledge of the student.
The Orlando Section extends its gratitude to Darlene Slattery and DK Weerasinghe for judging the fair and awarding the Avogadro Award along with thanks to the Pensacola Section and the South Florida Section of ACS for contributing to the monetary award for the prize.
Abstract
Prior research has indicated that the synthetic peptide D-(KLAKLAK)2 and its analogues (D-KLAKLAK and D-KLAK) exhibit potent cancer toxicity (oncotoxicity) and pro-apoptotic activity when internalized in mammalian cancer cells. The limitations of these peptides as therapeutic agents, however, are cancer specificity and membrane permeability. Research on tumor-homing peptides to attach to these kinds of peptides has had relative success in conferring specificity, but remain inefficient in promoting membrane permeability. Therefore, the only remaining problem is membrane permeability. The study conducted investigates chemical grafting of IP+ (imidazopyridinium) on to D-(KLAKLAK)2 and its analogues, and its effect on cellular permeability. IP+ is a heterocycle designed to facilitate the diffusion of large peptides across the cell membrane, and this study tested if grafting IP+ onto D-(KLAKLAK)2 and its analogues would improve its ability to diffuse across the cell membrane, which could aid in the development of a cancer therapeutic based on this peptide or others. Experimental methods included preparing D-(KLAKLAK)2 and its analogues, and grafting IP+ and a chloroalkane tag onto them. The effects of IP+ grafting were evaluated by running Chloroalkane Penetration Assays (CAQPA) on HEK293 cells in order to assess to what degree the peptides with or without IP+ could access the cytosol of the cells. Results indicated that IP+ significantly enhanced the intracellular localization of D-(KLAKLAK)2 and D-KLAK compared to controls lacking IP+. These results support the hypothesis and suggest that combining D-(KLAKLAK)2, a tumor-targeting peptide, and IP+ may provide a promising approach for developing broad-spectrum cancer therapeutics in the future.