Designed gramicidin-inspired stabilized peptide-based therapeutics to potentiate immunotherapy against aggressive kidney cancer.

ABSTRACT: This study reports engineered protease-stable, gramicidin-inspired, peptide-based proton transporter LD8Δ, with alternating L- and D-amino acid residues, to treat the highly chemoresistant, radioresistant, immunosuppressive metastatic renal cell carcinoma (RCC) cell line SK-RC-45. Exploiting the potential of the LD8Δ proton transporter, this study proposes mechanistically rational combination therapy with high translational potential. Current treatment methods involve multi-targeted tyrosine kinase inhibitors, which are accompanied by serious side-effects and exhibit an alarmingly low median overall survival. Computational and experimental data suggested that LD8Δ induced considerable membrane deformation, which supported the destabilization of the intracellular pH regulating mechanism obs

SUBMITTER: Mallick AM 

PROVIDER: S-EPMC12146981 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature