The isolation and biological activity of naturally occurring thymosin .alpha..sub.1 is described in U.S. Pat. No. 4,079,127 (Goldstein et al.). Thymosin .alpha..sub.1 is a component of thymosin fraction 5 which is a potent immunopotentiating preparation which has shown clinical effectiveness in increasing T-cell numbers and normalizing immune function in children with thymic dependent primary immunodeficiency diseases and can increase T-cell numbers in immunodepressed cancer patients. Thymosin .alpha..sub.1 has been found to be 10 to 1000 times more active than fraction 5 in several in vitro and in vivo assay systems designed to measure T-cell differentiation and function.
The chemical synthesis of thymosin .alpha..sub.1 by both solution phase and solid phase (using benzhydrylamine resin) synthetic procedures is described in U.S. Pat. No. 4,148,788 (Wang). Such procedures either employ intermediates containing acetylserine as the N-terminal group or are acetylated prior to removal of protective groups and cleavage from the resin.
An alternative solution phase synthesis of thymosin .alpha..sub.1 is described by Birr and Stollenwerk, Angew. Chem. 18, 394 (1979) which also employs blocked N-terminus intermediates. Applicant, in a talk presented at the Fifteenth European Peptide Symposium, Gdansk, Poland in September 1978 described the use of the 9-(2-sulpho)fluorenylmethyloxycarbonyl group as a reagent for the purification of synthetic peptides. During this talk it was indicated inter alia that the purification method was applied to preparing desacetylthymosin .alpha..sub.1. No indication of any biological or other utility for this compound was stated. The Proceedings of the Fifteenth European Peptide Symposium, Edited by Siemion and Kupryszewski (Wroclaw University Press--Wroclaw, Poland) was published in June 1979 and contained a paper by applicant entitled "The 9-(2-Sulpho)fluorenylmethyloxycarbonyl Group, A New Reagent for the Purification of Synthetic Peptides", which contained the following statement:
"We have recently applied the method to synthetic des-acetyl thymosin .alpha..sub.1. In this case the Sulfmoc-peptide was decomposed directly on the DEAE-cellulose column with 5% aqueous Et.sub.3 N and then eluted with 1M formic acid. This simple one-step procedure gave a dramatic improvement in the homogeneity of the product."
Additionally, applicant in conjunction with eight co-authors presented the Alan E. Pierce Award Lecture on Solid Phase Peptide Synthesis at the 6th American Peptide Symposium on June 20, 1979 which was published in December 1979 and which contained the following statement:
"This technique has been applied to several small neutral, acidic and basic peptides and to synthetic des-acetylthymosin .alpha..sub.1, a 28-residue peptide containing several acidic and basic residues. In the latter case, the homogeneity of the peptide was dramatically improved by this simple one-step procedure (FIG. 2)."
Recently there has been an indication in the press (Wall Street Journal, Mar. 10, 1980) that a synthetic gene for thymosin .alpha..sub.1 had been constructed, inserted into a plasmid, the recombinant plasmid inserted into E. coli and the cloned gene expressed to yield a material which was identified as thymosin .alpha..sub.1. However, it is likely that the gene product was N.sup..alpha. -desacetylthymosin .alpha..sub.1. Similarly, it is believed that natural thymosin .alpha..sub.1 is expressed as N.sup..alpha. -desacetylthymosin .alpha..sub.1 and then by post translation modification is converted to thymosin .alpha..sub.1.
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