Immunosuppressory activity of the cyclodimeric peptide with RGD-sequences

Our previous studies showed that the nonapeptide fragment of HLA-DQ of the sequence H-Thr-Pro-Gln-Arg-Gly-Asp-Val-Tyr-Thr-OH, located in the beta 164- 172 loop, strongly suppresses the humoral and cellular immune responses, wh ile its shorter analogs, H-Arg-Gly-Asp-Val-OH, H-Arg-Gly-Asp-Val-Tyr-OH and H-Gln-Arg-Gly-Asp-Val-Tyr-OH show only a weak stimulatory activity in resp ect to the humoral immunological response. These fragments contain the Arg- Gly-Asp (RGD) sequence, known for its importance for cellular association p henomena. Based on the crystal structure of HLA-DR1, we also des signed and synthesized a cyclic analog H-Cys-Arg-Gly-Asp-Val-Tyr-Cys-OH with restrict ed conformation, which strongly suppresses the immune response and selectiv ely inhibits the alphav beta3 integrin, suggesting that the mechanism of th e immunosuppressory action of the peptide is associated with inhibition of the integrin. In this paper we present the design and synthesis of the cycl odimeric peptide, Arg-Gly-Asp-Arg-Gly-Asp, which is also known as a selecti ve alphav beta3 inhibitor. The synthesized peptide strongly suppresses both the humoral and cellular immune response. The results support our hypothes is that the immunomodulatory activity of HLA-DQ fragments may be connected with their interactions with some particular integrins on the cell surface.