Cxcl Kemokı̇n ÖncüL Dı̇zelerı̇nden Türevlenen Küçük Peptı̇t MoleküLlerı̇nin İmmün Düzenleyı̇cı̇ Etkı̇sinin Değerlendirmesı̇

Abstract

Peptide structured small molecules function in the regulation of a variety of physiological processes and intercellular communication. In this study, precursor sequences of known 17 CXCL chemokine molecules were analyzed through a rationalistic and genuine algorithm. Small peptide molecules derived from these precursor sequences were determined and those (15 out of 17 molecules) which are appropriate for synthesis and in vitro testing were selected. The effects of these molecules on activation, proliferation and cytokine synthesis of immune cells in peripheral blood were assayed in the presence of various stimulants. Small peptide molecules derived from CXCL chemokine precursors (11 molecules) were determined with a potential to modulate immune responses. Three molecules (Pep8, Pep14, Pep17-2) determined to possess the highest impact were synthesized and labeled with fluorescein and data were gathered on their interaction with specific types of immune cells. In conclusion, our study was demonstrated that many peptide derivatives synthesized affect the immune responses in different aspects and various sensitivities. These small peptide molecules interacted with especially myeloid cells. These interaction capacities of small peptide molecules were considered to be candidates for targeting acute myeloid leukemia (AML) cells. The highest interaction between peptides and AML cell lines was observed between Pep14 and THP-1, which is a monocytic subgroup of AML cell lines. We observed that CD11bhigh cells more prone to uptake these peptides compared to CD11blow ones. These small peptides specific endocytosis mechanisms were evaluated and it was observed that they can use all endocytic pathways.