Immunomodulatory activity of conformationally restricted peptides related to TGF-beta-2 90-99 sequence.

Continuing our research on the immunomodulatory activity of the peptides related to the proteins of TGF-beta family, we have synthesized and investigated by Jerne's plaque forming cell (PFC) test and delayed type hypersensitivity (DTH) test the following linear peptides and their cyclic (disulphide-bridged) analogues: Lys-Thr-Pro-Lys-Ile (Ia) and Cys-Lys-Thr-Pro-Lys-Ile-Cys (Ib), Tyr-Ile-Gly-Lys-Thr-Pro (IIIa) and Cys-Tyr-Ile-Gly-Lys-Thr-Pro-Cys (IIIb), Tyr-Ile-Gly-Lys-Thr-Pro-Lys-Ile (IVa) and Cys-Tyr-Ile-Gly-Lys-Thr-Pro-Lys-Ile-Cys (IVb), Tyr-Tyr-Ile-Gly-Lys-Thr-Pro-Lys-Ile-Glu (Va) and Cys-Tyr-Tyr-Ile-Gly-Lys-Thr-Pro-Lys-Ile-Glu-Cys (Vb). It has been found that the insertion of the sequence of Ia into the disulphide bridged Ib generates a product with enhanced immunosuppressive activity. The similar procedure applied to IIIa, IVa and Va produces cyclic peptides devoid of any activity or of a diminished activity in DTH test. The exchange of Pro residue of Ia D-Pro resulted in the analogue IIa with a preserved immunosuppressive activity. The disulphide-bridged peptide IIb, a cyclic analogue of IIa, exhibited the same activity as IIa in both: PFC and DTH tests.