Thymosins

Literature References: Family of thymic peptide hormones that regulate immune and endocrine events. Extraction from calf thymus and partial purification: A. L. Goldstein et al., Proc. Natl. Acad. Sci. USA 56, 1010 (1966). Purification and characterization of thymosins and isoln of one of the active components, thymosin fraction 5: eidem, ibid. 69, 1800 (1972). Improved isoln and properties: J. A. Hooper et al., Ann. N.Y. Acad. Sci. 249, 125 (1975). Thymosin fraction 5 is a mixture of polypeptides ranging in mol wt from ~1000 to 15,000; it has a very low content of non-protein material; it is heat stable up to 80°. It is an immunopotentiating agent that can act in place of the thymus gland in immuno-deprived or thymus-deprived patients to restore some immune functions. Nomenclature of the polypeptide fragments of fraction 5 is based on isoelectric points: a-region below 5.0, b-region 5.0-7.0, and g-region above 7.0. Thymosin a1 is an acidic (pI 4.2), 28 amino acid polypeptide (mol wt 3108) found in the highly acidic region of fraction 5. It is a biologically active proteolytic fragment of prothymosin a1. Isoln and preliminary structural determination of thymosin a1: A. L. Goldstein et al., Proc. Natl. Acad. Sci. USA 74, 725 (1977). Isoln, characterization, biological activities, and amino acid sequence analysis of a1 and polypeptide b1, a 74 amino acid peptide identical with ubiquitin, q.v.: T. L. K. Low et al., J. Biol. Chem. 254, 981 (1979); T. L. K. Low, A. L. Goldstein, ibid. 987. Synthesis of a1 by solution methods: S. S. Wang et al., J. Am. Chem. Soc. 101, 253 (1979). Thymosin b4 is a biologically active, G-actin sequestering peptide consisting of 43 amino acids; mol wt 4.9 kDa; pI 5.1. Amino acid sequence of b4: T. L. K. Low et al., Proc. Natl. Acad. Sci. USA 78, 1162 (1981). Automated solid phase synthesis of b4: S. S. Wang et al., Int. J. Pept. Protein Res. 18, 413 (1981). Role of b4 in wound healing: K. M. Malinda et al., J. Invest. Dermatol. 113, 364 (1999). Series of articles on prepn, purification and characterization of thymic hormones and peptides: Methods Enzymol. 116, 213-291 (1985). Review of immune and endocrine modulation: P. H. Naylor, A. L. Goldstein, Adv. Pigment Cell Res. 256, 489-502 (1988); of immunological activities and therapeutic uses of thymic hormones and factors: S. Ben-Efraim et al., Crit. Rev. Immunol. 19, 261-284 (1999); of b-thymosins: V. T. Nachmias, Curr. Opin. Cell Biol. 5, 56-62 (1993); T. Huff et al., Int. J. Biochem. Cell Biol. 33, 205-220 (2001).

Literature References: Synthetic peptide; mol wt 3108. Synthesis: S. S. Wang et al., Int. J. Pept. Protein Res. 15, 1 (1980). Clinical trial in influenza vaccine enhancement: S. Gravenstein et al., J. Am. Geriatr. Soc. 37, 1 (1989). Clinical pharmacokinetics: K. L. Rost et al., Int. J. Clin. Pharmacol. Ther. 37, 51 (1999). Review of use in combined chemo-immunotherapy in treatment of cancer: E. Garaci et al., Int. J. Immunopharmacol. 22, 1067-1076 (2000); of clinical efficacy in hepatitis: P. H. Naylor, Expert Opin. Invest. Drugs 8, 281-287 (1999); A. Billich, Curr. Opin. Invest. Drugs 3, 698-707 (2002).