Research Focuses
Chemical Biology and Cancer Research:
We explore the intricate roles of enzyme inhibition and protein modification in cancer biology. Our lab specializes in designing and synthesizing novel small molecule inhibitors that target key enzymes involved in cell proliferation and survival. We investigate the biochemical and structural interactions of these inhibitors, providing insights into their potential as therapeutic agents. Our work in this area is contributing to the development of targeted cancer therapies that can modulate critical pathways with high specificity and efficacy.
Protein Modification and Regulatory Mechanisms:
Our research also delves into post-translational modifications, such as lysine acetylation, and their impact on protein function in disease contexts like inflammation and cancer. We employ synthetic chemistry to create novel chemical probes and conjugates that selectively modify proteins, enabling us to study the regulatory roles of these modifications in cellular processes. This approach helps to bridge the gap between chemical synthesis and biological function, offering new perspectives on how protein modifications influence disease progression.
Drug Delivery and Bioavailability Enhancement:
Improving the pharmacokinetics and bioavailability of therapeutic agents is a central theme in our lab. We are actively engaged in the synthesis of drug conjugates and polymeric formulations that enhance solubility, stability, and targeted delivery. By modifying existing drug molecules and creating novel delivery systems, we aim to overcome the limitations of conventional therapies, leading to improved treatment outcomes. Our work in drug delivery not only enhances the therapeutic potential of existing drugs but also paves the way for the development of new delivery platforms.
Biophysical Characterization and Mechanistic Studies:
We apply advanced biophysical techniques, including spectroscopy and mass spectrometry, to characterize the molecular interactions and mechanisms of the compounds we design. These studies provide a detailed understanding of how small molecules and biomolecular conjugates interact with their targets at the molecular level. Our findings contribute to a deeper understanding of drug mechanisms and inform the rational design of more effective therapeutics.
Publications
We investigated the potential of salicylate derivatives of naproxen as inhibitors of dihydrofolate reductase (DHFR), an enzyme crucial for nucleotide synthesis and cell proliferation. By synthesizing these derivatives, we aim to explore their ability to competitively inhibit DHFR, similar to the action of chemotherapy drugs like methotrexate. Utilizing biochemical, biophysical, and structural methods, we have characterized the binding affinity and inhibitory potency of these compounds. Our findings highlight the potential of these derivatives as promising candidates for novel cancer therapies that target DHFR.
Investigated the role of lysine acetylation within the NF-κB transcription factor complex, crucial for inflammation and cancer research. Synthesized a derivative of Aspirin using N-Hydroxysuccinimide, creating Aspirin-NHS ester to selectively target lysine residues. Conducted in a model protein system using β-Conglycinin, offering insights into the regulatory dynamics of NF-κB. This research enhances our understanding of protein acetylation modulation and NF-κB’s role in cancer, bridging chemical synthesis and biological investigation.
Thiols are essential biomolecules involved in many biological processes and can be reversibly modified by electrophilic compounds through a mechanism known as the “thiol switch.” We investigate the role of thiol- sensitivity in modulating the bioavailability and efficacy of drug candidates using an aspirin-cysteine conjugate. Aspirin is a well-known anti-inflammatory agent (NSAID), and cysteine is an amino acid that contains a thiol group and is involved in redox signaling and other important cellular processes. The conjugate was synthesized using a thioester linkage, which can act as a thiol switch that is sensitive to changes in the redox environment of the cell.
Conjugation And Evaluation of Novel Polymeric Naproxen-PEG Esters
We performed & researched organic synthesis methods to perform the esterification of naproxen to polyethylene glycol, to improve the aqueous solubility of naproxen. Thin-layer chromatography studies confirmed an decrease in the logP value. Spectrophotography drug release and solubility tests of the conjugate form reveal a prolonged release time. This indicates the successful development and distribution of the novel molecule. The lower logP value also corresponds to better oral absorption and uptake, therefore, naproxen-PEG ester demonstrates capacity as a drug delivery system with increased therapeutic efficacy.