Overview
Research in our laboratory focuses on the intersection of organic, inorganic, and medicinal chemistry, with a primary emphasis on photoactivated chemical probes and therapeutic agents. We develop light-controlled molecules that enable precise regulation of biological processes, with promising applications in enzyme inhibition and cancer therapy. Alongside this, we design and synthesize novel chelators and semi-synthetic proteins for the selective recovery of valuable metals from complex matrices like coal fly ash. Our work in this area emphasizes sustainable and recyclable systems, particularly for capturing metals such as nickel, copper, and lanthanides. We are also involved in the synthesis and biological investigation of natural products, focusing on cyanobacterial metabolites that are difficult to access. Our methods facilitate high-purity production, supporting environmental detection and biological research. Together, these efforts reflect our lab’s commitment to advancing chemical science and addressing critical challenges in health and environmental sustainability.
Photoactivated Chemical Probes and Therapeutics
A major focus of the Kodanko laboratory is to develop new molecules that can be activated with light. In this method enzyme inhibitors or other bioactive compounds are caged and released with light, leading to high levels of selectivity for enzyme inhibition under light vs. dark conditions. This method provides a novel way to achieve spatial and kinetic control over enzyme activity for chemical biology and anticancer applications. Recent work from our laboratory proved our method can be applied to inhibitors of the cysteine protease cathepsin B, an enzyme overexpressed in cancer and other human disease states, as well as cytochrome P450 enzymes CYP17A1 and CYP3A4 involved in biosynthesis and human drug metabolism. Compounds that display dual action properties, including photorelease and photosensitization have been applied successfully in cell models of human diseases.
Chemical Biology
Research in the Kodanko laboratory encompasses chemical synthesis, biochemical and pharmacological characterization and cell biology. Compounds synthesized in the Kodanko laboratory are evaluated in house and by working with collaborators to characterize their activity in various cell model of human diseases. Recent effort have focused on characterizing Ru(II) complexes that show photorelease and photosensitization properties that are activated by light to induce cell death in cancer cells, photochemotherapy agents for cancer, and emissive probes for enzymes. Experimental techniques commonly employed by researchers in the Kodanko laboratory include enzyme inhibition and cell viability assays, cellular imaging and flow cytometry. These techniques are used to study how our compounds act in cells and elicit cell death, either alone or in combination with other chemotherapeutics.
Selective Metal Recovery Using Novel Chelators and Semi-Synthetic Proteins
Our lab also focuses on designing novel chelators and semi-synthetic proteins to selectively recover valuable metals from complex matrices like coal fly ash (CFA). We developed SG-20, a chelator with high selectivity for Ni(II) over other metals. SG-20 forms complex clusters, making it effective for Ni recovery in various settings. We extended this work by creating Mb-SG-20, a semi-synthetic protein where SG-20 is conjugated to myoglobin. Mb-SG-20 efficiently captures Ni and Cu ions from CFA leachate and is recyclable, maintaining performance across multiple cycles. Additionally, we engineered MbD, a myoglobin conjugate with diethylenetriaminepentaacetic acid (DTPA), to capture lanthanides like EuIII. MbD facilitates efficient lanthanide recovery through a simple liquid extraction process, demonstrating over 90% capture from CFA leachate and adhering to green chemistry principles. Our research advances sustainable metal recovery technologies.
Natural Product Synthesis and Biological Investigation
Our lab specializes in the synthesis and study of natural products, focusing on cyanobacterial metabolites with limited commercial availability and poorly understood biological effects. We use solution-phase peptide synthesis to generate compounds such as Anabaenopeptin A, D, J, 679, and Ferintoic Acid A. These metabolites are difficult to access, hindering environmental detection and biological research, which is crucial for public health and wildlife protection in affected regions. Our synthesis approach is efficient, using a shared precursor to create multiple analogs with minimal steps, even on a multi-gram scale. The late-stage addition of homo-tyrosine, the costliest amino acid in the process, is a key feature of our method. The synthesized products achieve up to 97% purity, making them suitable as analytical standards and for biological testing. We are currently scaling up production to support more extensive biological investigations, particularly into aerosolized toxins. Our work aims to improve environmental monitoring and uncover new bioactivities, contributing to a better understanding of these natural products.