Phage Display Coupled with Computational Analysis for Identification of Transferrin-Binding Peptides

Transferrin, an iron-transporting human serum protein, has recently emerged as a versatile carrier for drug delivery to tumors or for transport across the blood-brain barrier. Conjugating hTf-binding peptides to therapeutic agents is a promising strategy for targeted drug delivery. Therefore, we screened high-affinity human serum transferrin (hTf)-binding peptides using phage display technology to identify candidate binders, established quantitative criteria for bio-panning assessment and binding-affinity constants from experimentally quantified phage titers rather than clonal sequencing to support objective evaluation, and used structural bioinformatics docking approaches to characterize the molecular interactions between the phage display-derived dodecapeptides and transferrin. These methods linked screening, quantification, and docking to candidate identification and interaction characterization, enabling identification of hTf-binding peptides as a robust platform for transferrin receptor-mediated targeted drug design and clinical translation of targeted therapeutics.