BPC-157 Predicted to Bind SH3 Domains and Activate Src Family Kinases: In Silico Modeling and Fluorescent Fusion Protein Validation

Body Protection Compound-157 (BPC-157) is a synthetic pentadecapeptide derived from human gastric juice with regenerative and cytoprotective effects reported across diverse tissues. Despite extensive preclinical study, the precise molecular mechanism underlying BPC-157's pleiotropic pro-repair effects remains incompletely understood. A key unresolved question is whether BPC-157 acts through extracellular receptor engagement, via intracellular interactions, or through a combination of both. Drawing on preclinical literature, structural modeling, and in silico docking, I propose that BPC-157 adopts a polyproline II helix that engages the Src homology 3 (SH3) domains of Src family kinases (SFKs; c-Src, Yes, Fyn). This interaction relieves SH3 domain-mediated autoinhibition of SFKs, resulting in focal adhesion kinase (FAK)-extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling cascades. To enable future experimental validation, a custom baculovirus encoding an engineered mCherry-BPC157 ₂ fusion protein was generated and used to transduce Sf9 cells. Expression of mCherry-BPC157 ₂ was validated by fluorescent imaging and confirmed by western blot at the expected molecular weight (~31 kDa). Collectively, this work proposes a novel structural and functional mechanism for BPC-157, provides in silico docking support, and introduces a molecular tool to probe the BPC-157 interactome.