Defensins are a large and ancient family of host–defence peptides present across vertebrates, invertebrates, and plants, where they play a crucial role in innate immunity. Among them, big defensins represent a structurally distinctive subfamily characterized by a hydrophobic N‐terminal domain and a cysteine‐rich C‐terminal β‐defensin‐like domain. Here, we report the synthesis, structural characterization, β‐Cyclodextrin–polymer interaction, and biological evaluation of a newly N‐terminal peptide fragment AVPDVAFNAYG ( BD11 ) of the parent RPD‐1 protein isolated from of the bivalve Ruditapes philippinarum . To date, no information has been available regarding the structural or functional properties of this undecapeptide, which shows no homology with other known defensins. Biophysical characterization was carried out to investigate the conformational behavior as well as the ability of BD11 to interact with membranes. We also evaluated its biological potential through antimicrobial, cell toxicity, and mobility assays. A conjugated derivative with a hydrophobic adamantane group attached to the N‐terminus via a PEG linker was synthesized to assess the drug‐delivery potential upon complex formation with a water‐soluble β‐cyclodextrin polymer (6‐deoxy‐6‐(2‐carboxyethyl)thio‐β‐cyclodextrin polymer, SuBCDPS ) and to enable comparative biological testing. Our findings provide new insights into the structure–function relationship of this short peptide and highlight its potential as a cell migration inhibitor.
Turnaturi et al. (Mon,) studied this question.