Tuftsin, Thr-Lys-Pro-Arg. Anatomy of an Immunologically Active Peptide

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 1981 Dec 4

PMID 7035869

Citations 7

Authors

M Fridkin

P Gottlieb

Affiliations

Soon will be listed here.

Abstract

Tuftsin, a natural occurring tetrapeptide, has been found to exhibit several biological activities connected with immune system function. Although little is known about tuftsin's 'biogenesis', much information has been gleaned about its structure-function relationships, which have shown that several features of the molecule are essential for expression of full biological activity. Furthermore, specific receptor sites for tuftsin have been found to exist exclusively on phagocytic cells. Research indicates that tuftsin binding to target cells effect intracellular calcium and cyclic nucleotide levels. Implication of these facts on tuftsin's mode of action are discussed. Basic peptidic segments resembling tuftsin are found in a variety of regulatory peptides. Questions are, therefore, raised as to the biospecificity an cross-reactivity of these sequences. Substance P, one such peptide, which binds with and activates tuftsin receptors, is described. In light of tuftsin's therapeutic potential, assays for its determination have been introduced. When applied to analyze human blood serum of normal as well as of various pathological origins, direct correlation was found between tuftsin levels and susceptibility to bacterial infections.

Citing Articles

Helminth-Based Product and the Microbiome of Mice with Lupus.

Neuman H, Mor H, Bashi T, Givol O, Watad A, Shemer A mSystems. 2019; 4(1).

PMID: 30801028 PMC: 6381224. DOI: 10.1128/mSystems.00160-18.

Therapeutic effects of a synthetic peptide of C-reactive protein in pre-clinical tumor models.

Barna B, Eppstein D, Thomassen M, Nestor Jr J, Ho T, Medendorp S Cancer Immunol Immunother. 1993; 36(3):171-6.

PMID: 8439977 PMC: 11038124. DOI: 10.1007/BF01741088.

Antibacterial properties of tuftsin and its analogs.

Muzalewski F, Konopinska D Antimicrob Agents Chemother. 1984; 25(1):134-6.

PMID: 6703677 PMC: 185452. DOI: 10.1128/AAC.25.1.134.

Potentiation of the defective monocyte chemotaxis in Hodgkin's disease by in vitro tuftsin treatment.

Lukacs K, Berenyi E, Kavai M, Szegedi G, SZEKERKE M Cancer Immunol Immunother. 1983; 15(2):162-3.

PMID: 6553514 PMC: 11039023. DOI: 10.1007/BF00199710.

Tuftsin (Thr-Lys-Pro-Arg), a natural modulator of macrophage activity: further studies.

Bump N, NAJJAR V Mol Cell Biochem. 1984; 63(2):137-42.

PMID: 6493218 DOI: 10.1007/BF00285221.

References

Stern M, Warshawsky A, Fridkin M . Facile thiolytic removal of the o-nitrophenylsulphenyl amino-protecting group. Int J Pept Protein Res. 1979; 13(3):315-9. DOI: 10.1111/j.1399-3011.1979.tb01885.x. View

Bar-Shavit Z, Goldman R, Stabinsky Y, Gottlieb P, Fridkin M, Teichberg V . Enhancement of phagocytosis - a newly found activity of substance P residing in its N-terminal tetrapeptide sequence. Biochem Biophys Res Commun. 1980; 94(4):1445-51. DOI: 10.1016/0006-291x(80)90581-1. View

NAJJAR V . Defective phagocytosis due to deficiencies involving the tetrapeptide tuftsin. J Pediatr. 1975; 87(6 Pt 2):1121-4. DOI: 10.1016/s0022-3476(75)80125-9. View

Maganiello V, Vaughan M . Prostaglandin E 1 effects on adenosine 3':5'-cyclic monophosphate concentration and phosphodiesterase activity in fibroblasts (mouse L cells-tissue culture-enzyme kinetics-prostaglandin homologues). Proc Natl Acad Sci U S A. 1972; 69(1):269-73. PMC: 427589. DOI: 10.1073/pnas.69.1.269. View

Oroszlan S, Henderson L, Stephenson J, Copeland T, Long C, Ihle J . Amino- and carboxyl-terminal amino acid sequences of proteins coded by gag gene of murine leukemia virus. Proc Natl Acad Sci U S A. 1978; 75(3):1404-8. PMC: 411480. DOI: 10.1073/pnas.75.3.1404. View

Okamoto K, Shimamura S . [Synthesis of peptides related to tuftsin. I (author's transl)]. Yakugaku Zasshi. 1976; 96(3):315-20. DOI: 10.1248/yakushi1947.96.3_315. View

Chaudhuri M, NAJJAR V . Solid-phase tuftsin (Thr-Lys-Pro-Arg) synthesis: deprotection and resin cleavage with trifluoromethane sulfonic acid. Anal Biochem. 1979; 95(1):305-10. DOI: 10.1016/0003-2697(79)90220-3. View

Horsmanheimo A, Horsmanheimo M, Fudenberg H . Effect of tuftsin on migration of polymorphonuclear and mononuclear human leukocytes in leukocyte migration agarose test. Clin Immunol Immunopathol. 1978; 11(3):251-5. DOI: 10.1016/0090-1229(78)90048-x. View

Nishioka K, Constantopoulos A, SATOH P, NAJJAR V . The characteristics, isolation and synthesis of the phagocytosis stimulating peptide tuftsin. Biochem Biophys Res Commun. 1972; 47(1):172-9. DOI: 10.1016/s0006-291x(72)80025-1. View

10.

Erickson W, BURGERT Jr E, Lynn H . The hazard of infection following splenectomy in children. Am J Dis Child. 1968; 116(1):1-12. DOI: 10.1001/archpedi.1968.02100020003001. View

11.

Chang D, Greibrokk T, Knudsen R, Howard G, Humphries J, Folkers K . Differentiation of factor C-LHIH and the synthetic contraceptive polypeptide, H-Thr-Pro-Arg-Lys-OH. Biochem Biophys Res Commun. 1975; 65(4):1208-13. DOI: 10.1016/s0006-291x(75)80358-5. View

12.

Konopinska D, Nawrocka E, Siemion I, Szymaniec S, SLOPEK S . Tuftsin and its analogues. III. Modification of basic amino acid residues in the peptide chain. Arch Immunol Ther Exp (Warsz). 1979; 27(1-2):151-7. View

13.

NAJJAR V, Constantopoulos A . A new phagocytosis-stimulating tetrapeptide hormone, tuftsin, and its role in disease. J Reticuloendothel Soc. 1972; 12(2):197-215. View

14.

Blumenstein M, Layne P, NAJJAR V . Nuclear magnetic resonance studies on the structure of the tetrapeptide tuftsin, L-threonyl-L-lysyl-L-prolyl-L-arginine, and its pentapeptide analogue L-threonyl-L-lysyl-L-prolyl-L-prolyl-L-arginine. Biochemistry. 1979; 18(23):5247-53. DOI: 10.1021/bi00590a032. View

15.

Henderson L, Gilden R, Oroszlan S . Amino acid sequence homology between histone H5 and murine leukemia virus phosphoprotein p12. Science. 1979; 203(4387):1346-8. DOI: 10.1126/science.218289. View

16.

Fidalgo B, Katayama Y, NAJJAR V . The physiological role of the lymphoid system. V. The binding of autologous (erythrophilic) gamma globulin to human red blood cells. Biochemistry. 1967; 6(11):3378-85. DOI: 10.1021/bi00863a007. View

17.

Lembeck F . [Central transmission of afferent impulses. III. Incidence and significance of the substance P in the dorsal roots of the spinal cord]. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1953; 219(3):197-213. View

18.

King H, SHUMACKER Jr H . Splenic studies. I. Susceptibility to infection after splenectomy performed in infancy. Ann Surg. 1952; 136(2):239-42. PMC: 1802258. DOI: 10.1097/00000658-195208000-00006. View

19.

Bar-Shavit Z, Bursuker I, Goldman R . Functional tuftsin binding sites on macrophage-like tumor line P388D1 and on bone marrow cells differentiated in vitro into mononuclear phagocytes. Mol Cell Biochem. 1980; 30(3):151-5. DOI: 10.1007/BF00230168. View

20.

NAJJAR V . Molecular basis of familial and acquired phagocytosis deficiency involving the tetrapeptide, thr-lys-pro-arg, tuftsin. Exp Cell Biol. 1978; 46(1-2):114-26. DOI: 10.1159/000162886. View