NSF-Backed Research Transforms Understanding of Peptide Therapeutics in Drug Delivery Science

Copper accumulation destroys neurons in Alzheimer's patients and ravages livers in children with Wilson's disease. His academic research at Texas A&M University focused on deciphering how peptide-metal interactions could be harnessed for therapeutic design, research funded by the National Science Foundation that reshaped scientific understanding of metal-related disorders. His molecular-level investigations of methanobactin analogs have revealed binding mechanisms now cited internationally across studies of neurological diseases, cancer biology, and pharmaceutical formulations.​

Mapping Metal-Peptide Interactions Through Advanced Spectroscopy

Sesham developed pH-dependent methanobactin analog peptides that selectively chelate copper and zinc ions implicated in neurodegenerative conditions. Using ion-mobility mass spectrometry, he mapped how these engineered molecules change conformational structure when binding different metals at varying acidity levels. The technique enabled the simultaneous measurement of mass-to-charge ratios and collision cross sections, revealing which amino acid residues coordinate metal ions and how protonation states influence binding affinity.​

His findings demonstrated that cysteine thiolates, histidine imidazolates, and carboxylate termini serve as primary metal attachment points, with binding efficiency varying dramatically based on pH conditions. Sesham presented these structural insights at the 69th Southwest Regional Meeting of the American Chemical Society and multiple Texas A&M System research symposia, where his work was recognized for advancing understanding of metalloprotein biochemistry. The Welch Foundation awarded him research scholarships supporting this investigation into peptide-metal interaction chemistry.​

Therapeutic Applications for Neurological and Metabolic Diseases

In controlled laboratory models, methanobactin peptides have been shown to remove excess copper from liver cells. Sesham's analog designs targeted diseases, including Wilson's disease, where genetic defects prevent copper excretion, and Menkes disease, where copper transport mechanisms malfunction. His research also examined the applications of copper ions in Alzheimer's disease, where they act as protein misfolding agents that accelerate the progression of neurodegeneration.​

Preclinical laboratory models demonstrated that methanobactin analogs effectively reduced copper overload, restoring mitochondrial function and mitigating cellular toxicity in controlled experimental settings. The peptides demonstrated improved metal selectivity and tolerability profiles in controlled experimental models. Sesham's systematic analysis of metal competition for binding sites established selectivity profiles for silver, lead, cobalt, iron, manganese, nickel, and zinc ions, providing pharmaceutical developers with data essential for therapeutic design.​

International Citations Drive Continued Investigation

Sesham authored 11 peer-reviewed papers in journals such as JoVE and the European Journal of Mass Spectrometry, documenting peptide binding kinetics and therapeutic mechanisms. His publications receive citations across the United States, European, and Asian research examining metal toxicity, nanomedicine formulation, and peptide pharmaceutical development. Recent studies on cuproptosis in Alzheimer's disease and on the analytical characterization of peptide therapeutics, which reference methanobactin chelation strategies, have further elucidated these mechanisms originally characterized by Sesham.​

Scientists at institutions including UC Davis now employ similar ion-mobility mass spectrometry techniques to address formulation challenges in peptide-based medicines, methods Sesham refined during his Texas A&M investigations. His structural models of copper-bound methanobactin, which show pyramid-like conformations with metal ions at the base, inform current drug delivery research. The field has grown substantially since his graduate work, with over 100 peptide-based drugs now available in the United States, treating conditions from diabetes to multiple sclerosis.