Development and synthesis of a non-specific immunomodulating peptidomimetic
- DOI
- 10.5922/vestniknat-2026-2-6
- Pages
- 95-107
Abstract
The use of peptides is associated with certain challenges. Due to proteolytic instability and a short plasma half-life, peptides require the development and application of specialized delivery systems, which often limits their use to parenteral administration routes. Low bioavailability following oral administration further complicates the clinical use of peptides, especially in chronic diseases requiring patient-friendly treatment regimens. The aim of the study was to develop, synthesize, and characterize a peptidomimetic for oral administration with nonspecific immunomodulatory activity, as well as to assess its cytotoxicity and effect on DC proliferation. The object of the study was a peptidomimetic designated CD-17 with the following amino acid sequence: CTSIGGAGTCPPICFFD. It was established that there are no matches between the amino acid sequence of CD-17 and known peptides or peptidomimetics, which indicates the uniqueness of the developed peptidomimetic. The physicochemical properties and structure of the peptidomimetic were predicted. According to the APD database, the total net charge of CD-17 is – 1, the peptide hydrophobicity according to the Wimley–White method (i. e., the sum of the transfer energy of the peptide without the whole residue from water to the POPC interface) is 0.86 units, the molecular weight is 1688.97 Da, the molecular formula of the peptide is C73H109N17O23S3, and the protein-binding potential (Boman index) is 0.41 kcal/mol. It was established that CD-17 is a biologically active peptidomimetic and belongs to the DILI-negative category, i. e., it is safe for the liver. Prediction of the acute oral toxicity of CD-17 in rats demonstrated that the peptidomimetic does not exhibit acute toxicity (non-toxic at doses > 500 mg/ kg). The VDss of CD-17 is 0.879 with an optimal range of 0.04—20, while Fu is 89.24 % with an optimal value of ≥ 20. CD-17 demonstrates excellent CL and a moderate half-life. It was established that after three days of cultivation with the peptidomimetic, the number of DCs was 23.07 % higher (p < 0.05) compared with the negative control.