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.
Wieczorek
Z
Z
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Słoń
J J
JJ
Siemion
I Z
IZ
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D003553:Cystine / Q000737:chemistry; D006462:Hemolytic Plaque Technique; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D016212:Transforming Growth Factor beta / Q000737:chemistry*
D000276:Adjuvants, Immunologic; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D016212:Transforming Growth Factor beta; D003553:Cystine