Receptor Binding, Functional Activity, and Cell Viability Assessment of Novel Marine-Based Hybrid Peptides from Raja porosa

The hybrid approach remains a compelling strategy for designing molecules that combine enhanced biological activity with a favorable safety profile. Marine peptides, in particular, have attracted significant attention due to their well-documented broad spectrum of biological activities. Peptides derived from rays have been recognized for their diverse biological activities. Notably, physicochemical properties of these peptides support practical application without requiring further refinement of the mature molecule or specialized formulations. In this study, we present two new chimeric peptides, PK01# and PK02#, which incorporate an opioid pharmacophore linked to a short amino acid sequence derived from the skate Raja porosa. Those compounds interact with the opioidergic system, specifically targeting the mu-opioid receptor (MOR). Furthermore, the compounds were evaluated for their effects on cancer cell viability through in vitro MTT assays (as an exploratory endpoint) and for their binding compatibility with EGFR via in silico docking. Both compounds showed limited effects on cell viability in HeLa, SAS, and PANC-1 cells, while PK02# induced a minor reduction in metabolic activity in glioblastoma cells without reaching IC50 values or significant cytotoxic thresholds. Interestingly, the structures of these hybrid compounds offer valuable insights into the role of phenylalanine residues within their sequences, which appear to be critical for both biological activity and receptor interaction. Moreover, these findings may support future structural optimization of peptide hybrids focused on receptor modulation and biological profiling.