Design of synthetic selenopeptides with antioxidant activity for the treatment of XP and non-melanoma skin cancer.

Introduction: Xeroderma Pigmentosum (XP) is a rare, autosomal recessive disorder characterized by extreme sensitivity to ultraviolet (UV) light. Current treatments primarily focus on symptom management and surgical tumor excisions. Selenopeptides, which possess a modified residue of Cysteine (Selenocysteine), are distinguished for their antioxidant and photoprotective properties. These properties could be beneficial in counteracting the oxidative DNA damage observed in XP lesions. Objective: Building upon the work initiated by the Brazilian SynBio UFG iGEM Design League team, this study aimed to develop a new approach for designing and expressing synthetic selenopeptides through in silico optimization, to target both XP and non-melanoma skin cancers. Methods: Five novel sequences of selenopeptides, named Selera, were designed and evaluated through bioinformatic tools. Selera-2 was chosen as the best model designed for its physico-chemical and structural properties and was submitted to docking analysis with therapeutic targets. Results and Discussion: Docking models of B-RAF and TrxR1 demonstrated to be the most stable binding sites, considering low-binding energy levels and molecular dynamics profile, suggesting possible targets for anti tumor effect. A new recombinant expression plasmid vector was proposed, p-Sec Reg 1, in order to ensure optimal expression for future trials and production. The in silico validation of this innovative approach allows the creation of novel selenopeptides and their prospective applications in the treatment of XP and other skin cancer conditions.