Dimerization of an Immunoactivating Peptide Derived from Mycobacterial hsp65 Using N-Hydroxysuccinimide Based Bifunctional Reagents Is Critical for Its Antitumor Properties

0387537 - MBÚ 2013 RIV US eng J - Článek v odborném periodiku
Bezouška, Karel - Kubínková, Z. - Stříbrný, J. - Volfová, B. - Pompach, Petr - Kuzma, Marek - Šírová, Milada - Říhová, Blanka
Dimerization of an Immunoactivating Peptide Derived from Mycobacterial hsp65 Using N-Hydroxysuccinimide Based Bifunctional Reagents Is Critical for Its Antitumor Properties.
Bioconjugate Chemistry. Roč. 23, č. 10 (2012), s. 2032-2041. ISSN 1043-1802. E-ISSN 1520-4812
Grant CEP: GA MŠMT 1M0505; GA ČR GA303/09/0477; GA ČR GD305/09/H008
Výzkumný záměr: CEZ:AV0Z50200510
Klíčová slova: HUMAN EOSINOPHILS * KILLER-CELLS * CD69
Kód oboru RIV: CE - Biochemie
Impakt faktor: 4.580, rok: 2012

We have shown previously that a short pentapeptide derived from the mycobacterial heat shock protein hsp65 can be highly activating for the immune system based on its strong reactivity with the early activation antigen of lymphocytes CD69. Here, we investigated an optimal form of presentation of this antigen to the cells of the immune system. Four different forms of the dimerized heptapeptide LELTEGY, and of the control inactive dimerized heptapeptide LELLEGY that both contained an extra UV active glycine-tyrosine sequence, were prepared using dihydroxysuccinimidyl oxalate (DSO), dihydroxysuccinimidyl tartarate (DST), dihydroxysuccinimidyl glutarate (DSG), and dihydroxysuccinimidyl suberate (DSS), respectively. Heptapeptides dimerized through DST and DSG linkers had optimal activity in CD69 precipitation assay. Moreover, dimerization of active heptapeptide resulted in a remarkable increase in its proliferation activity and production of cytokines in vitro. Furthermore, while DST and DSG dimerized heptapeptides both significantly enhanced the cytotoxicity of natural killer cells in vitro, only the DSG dimerized compound was active in suppressing growth of melanoma tumors in mice and in enhancing the cytotoxic activity of tumor infiltrating lymphocytes ex vivo. Thus, while the dimerization of the immunoactive peptide caused a dramatic increase in its immunoactivating properties, its in vivo anticancer properties were influenced by the chemical nature of linker used for its dimerization
Trvalý link: http://hdl.handle.net/11104/0216673