1.Immunoregulating peptides II. In vitro effects of TP5 analogs on E-rosette formation and cell division.
Denes L1, Szende B, Ember J, Major J, Szporny L, Hajos G, Nyeki O, Schon I, Lapis K, Kisfaludy L. Immunopharmacol Immunotoxicol. 1987;9(1):1-18.
The effects of seventeen synthetic analogs of thymopentin (TP-5) have been studied in the active and azathioprine-inhibited E-rosette tests. Thymopentin was gradually shortened from the C terminus to peptides and single amino acids. Thymopoietin 32-34 (Arg-Lys-Asp-RGH-0205-TP-3) (II) and thymopoietin 32-35 (Arg-Lys-Asp-Val-RGH-0206-TP-4) (I) were the most active peptides. Dipeptide Arg-Lys produced significant stimulatory effect on azathioprine (ED75) inhibited E-receptor. Treatment of azathioprine (ED75)-inhibited E-rosette forming cells (ERFC) with arginine or especially lysine increased the number of ERFC. Some of TP-4 analogs decreased further the number of ERFC decreased by azathioprine ED30. These "suppressive" peptides as well as TP-3 caused a partial arrest of K 562 cell proliferation up to 96 hours. Results suggest that TP-5 is not the smallest active fragment of thymopoietins, since peptides (TP-3 and TP-4) exhibit similar or higher T-cell membrane activation on E-receptor.
2.Thymopentin and splenopentin as immunomodulators. Current status.
Singh VK1, Biswas S, Mathur KB, Haq W, Garg SK, Agarwal SS. Immunol Res. 1998;17(3):345-68.
Splenopentin (SP-5, Arg-Lys-Glu-Val-Tyr) and thymopentin (TP-5, Arg-Lys-Asp-Val-Tyr) are synthetic immunomodulating peptides corresponding to the region 32-34 of a splenic product called splenin (SP) and the thymic hormone thymopoietin (TP), respectively. TP was originally isolated as a 5-kDa (49-amino acids) protein from bovine thymus while studying effects of the thymic extracts on neuromuscular transmission and was subsequently observed to affect T cell differentiation and function. TP I and II are two closely related polypeptides isolated from bovine thymus. A radioimmunoassay for TP revealed a crossreaction with a product found in spleen and lymph node. This product, named splenin, differs from TP only in position 34, aspartic acid for bovine TP and glutamic acid for bovine splenin and it was called TP III as well. Synthetic pentapeptides (TP-5) and (SP-5), reproduce the biological activities of TP and SP, respectively. It is now evident that various forms of TPs were created by proteolytic cleavage of larger proteins during isolation.
3.Functional effects of splenin32-34 on antibody formation in immunosuppressed mice.
Diezel W, Eckert R, Forner K, Gruner S. Biomed Biochim Acta. 1986;45(10):1349-52.
Sublethally irradiated AB/Bln mice (500 cGy) were treated with splenotritin (fragment 32-34 of the splenic hormone splenin) and tested for their capability of producing antibodies against target sheep red blood cells. In x-ray plus splenotritin treated mice antibody forming cells were found earlier and in a higher frequency than in mice treated with x-rays alone.
4.The effect of thymopoietin 32-34 (TP3) on suramin-induced inhibition on delayed type hypersensitivity in guinea pigs.
Dénes L1, Hajós G, Szporny L, Szende B, Lapis K, Sipka S, Szegedi G. Immunol Invest. 1987 Jun;16(4):275-9.
Suramin administration inhibits virus replication and produces impaired immunoregulation. Delayed type hypersensitivity (DTH)-reaction was inhibited by Suramin (200 mg/kg, i.p.) injection in guinea-pigs immunized with BCG vaccine. Suramin-inhibited DTH-reaction was restored to normal level after 4 days of treatment with thymopoietin 32-34 (TP 3) and TP5 (1 mg/kg, i.p.), TP3 greater than TP5. TP3 produced the strongest restoration when applied together with Suramin, but a single treatment with TP3 or TP5 oligopeptide inhibited the development of DTH-reaction. TP3 with Suramin treatment might be advantageous to eliminate defective side effects of Suramin on immune system and TP3 with indirect inducing action on IL-2, IFN-gamma production may be useful in therapy of AIDS patients.
