Thymulin

1 Identity

Metal-peptide coordination complex, or, depending on what a supplier actually ships, a plain nonapeptide. The peptide portion is nine residues, all-L, free acid C-terminus, no cysteine, no disulfide, no aromatic residue and therefore no 280 nm chromophore, with a non-proteinogenic N-terminal pyroglutamate formed by cyclization of Glu1. Zinc, where present, is held in reversible pH-dependent 1:1 coordination and is not part of any covalent structure. The peptide and the complex are different chemical entities with different formulas and different masses, and the distinction is routinely blurred in commerce. The metal-free article is also sold as "serum thymic factor acetate", a second catalog name for the same peptide at the same vendor. No CAS number was verified and none is printed. Not synonyms: thymosin alpha-1 (thymalfasin), thymopentin.

Sequence

H-pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH (pyroglutamyl-AKSQGGSN). Nine residues, all-L, free acid C-terminus. The N-terminal pyroglutamate is formed by cyclization of Glu1 and is part of the identity, not an impurity. Zinc is not part of the sequence, and the sequence is complete without it, which is exactly why a sequence result cannot tell you which of the two commercially sold articles is in the vial. The residue string is printed here because two independent published sources give it and an in-house construction reproduces the published formula from it exactly.

Molecular formula

C33H54N12O15 (metal-free nonapeptide, free base). Zinc complex as the formal 1:1 species with two protons displaced: C33H52N12O15Zn. Acetate hydrate forms are what the reagent trade actually ships, and a supplier formula written C33H54N12O15 . XC2H4O2 [XH2O] contains no zinc at all, whatever the marketing copy on the same page says.

Average mass

Average mass 858.864 Da (C33H54N12O15), the metal-free nonapeptide as the free base. The zinc complex has no single defined molecular weight in the sense A covalent species does, and three different numbers circulate for it: the formal [peptide - 2H + Zn] species C33H52N12O15Zn computes to 922.228 Da; the naive additive figure 858.864 + 65.38 = 924.244 Da is what careless certificates print, and its 2.016 Da error is exactly the two displaced protons; and 858.864 is what an acidic reversed-phase LC-MS method returns whichever article was injected, because the mobile phase strips the metal. One reagent supplier prints 858.9 for its acetate hydrate article, which is the metal-free peptide.

Monoisotopic mass

858.38316 Da neutral (C33H54N12O15); [M+H]+ 859.39044. Formal zinc complex C33H52N12O15Zn, 920.29665 monoisotopic on 64Zn. One measurement genuinely does discriminate, and it is not the mass number but the isotope pattern: zinc's natural abundances are 64Zn 49.2, 66Zn 27.7, 67Zn 4.0, 68Zn 18.5 and 70Zn 0.6 percent, so a species that carries zinc into the gas phase shows an envelope no metal-free peptide can imitate. A method that dissociates the complex destroys that evidence before it reaches the detector, which is why the chromatographic conditions are part of the identity claim.

Salt / variant note

A genuine two-article name where the substitution is invisible to mass spectrometry, and unlike most such cases no arithmetic catches it. The forms that can arrive under this name are set out here, each with its own formula and mass. (1) metal-free FTS, C33H54N12O15, 858.864 / 858.38316. (2) the 1:1 zinc complex, formally C33H52N12O15Zn, 922.228 / 920.29665, or 924.244 on the naive additive model that forgets the two displaced protons. Because 0.1 percent TFA mobile phase dissociates the complex, both articles return 858.38 / 858.86 on routine ESI-MS: a certificate reporting 858.9 proves nothing about zinc in either direction, and only ICP-MS at a stated mol Zn per mol peptide, or a method demonstrated to preserve the complex so the zinc isotope envelope is visible, discriminates them. The market makes the point for us: the same supplier's article is sold as an acetate hydrate whose printed formula contains no zinc at all, on a page whose own text describes the compound as zinc-dependent. (3) A real arithmetic trap: the mono-acetate salt of the metal-free peptide, C35H58N12O17, 918.916 / 918.40429, sits only 3.31 Da below the formal zinc-complex figure of 922.228, so a rounded certificate or a low-resolution instrument cannot tell an acetate salt of the apo-peptide from a zinc complex. (4) second name, same molecule: a supplier carries both "Thymulin" and "Serum Thymic Factor Acetate" as separate catalog items. (5) open-chain Glu1 form, cyclization incomplete, C33H56N12O16, 876.879 / 876.39372, plus 18.011 Da. (6) des-Asn9 octapeptide, pGlu-AKSQGGS, C29H48N10O13, 744.760 / 744.34023. (7) blended zinc: post-synthesis addition of zinc acetate or chloride to metal-free peptide gives a passing total-zinc number with no complex present, which is why unbound zinc must be determined separately after ultrafiltration. Naming collisions with their own masses: thymosin alpha-1 3108.315, thymopentin 679.776, Thymogen and Thymagen 333.344, TB-500 889.018, and Thymalin, which has no mass at all.

2 Class & testing panel

Form

Single article

Testing panel

P5 — panel definitionas the zinc complex; it reverts to P1 if the supplier declares metal-free FTS

3 Primary sources & evidence

The index reports the design and provenance of the literature, not a conclusion about effect.

Literature exists, is old, is good of its kind, and is recorded by study type only. Structural characterization by NMR: PMID 3711109, J Biol Chem 1986, and PMID 3356698, J Biol Chem 1988. Biochemical: PMID 2413455, PNAS 1985, the zinc-dependent conformational epitope; PMID 18476235, Met Based Drugs 1994, the zinc-peptide interaction studied directly. Animal: PMID 6609827, Eur J Immunol 1984, mouse, marginal zinc deficiency; PMID 10811143, J Gerontol A Biol Sci Med Sci 2000. Experimental: PMID 19850345, Mol Immunol 2009, with zinc co-administration. Reviews: PMID 15003367, Peptides 2004; PMID 19236333, Ann N Y Acad Sci 2009; PMID 1418292, J Autoimmun 1992; PMID 24588820, Curr Pharm Des 2014, which frames the translational path as gene therapy in animal models. The human-data finding is an absence: no human therapeutic trial of administered thymulin was identified, reviews spanning 1992, 2004 and 2014 report none, and the human data in the literature concern endogenous levels as a biomarker rather than administered material. No NCT number was identified; the finding is that none was located, not that none exists. The evidence grade is D. Two further absences are recorded as absences: no immunogenicity data and no carcinogenicity assessment were identified, and for an agent supplied as a metal complex, cumulative metal exposure and copper-zinc balance are unaddressed in the literature located. One marketing claim is recorded solely as an absence of sources: for the heavily promoted hair-loss use of Zn-thymulin, no primary literature was identified at all, and naming that absence is the honest finding.

4 Storage & specification

Storage

Lyophilized powder, -20 degrees C plus or minus 5 degrees C, desiccated, protected from light and moisture. If the article is confirmed as the zinc complex the packaging chain is additionally controlled for chelators, since the coordination is reversible and pH-dependent: no EDTA-treated closures, no citrate-buffered desiccant sachets, and glass rather than any coated closure of unverified composition. Shipped frozen with a temperature logger in the carton.

Shelf life

The retest interval is 24 months at -20 degrees C plus or minus 5 degrees C, supported by the company's own stability data. Zinc stoichiometry is treated as a stability-indicating attribute and is re-run at every retest, because metal loss rather than backbone degradation is the first thing expected to move on a reversibly coordinated complex, and it is invisible in an area-percent purity figure. Open-chain Glu1 content at plus 18.011 Da is the second stability-indicating attribute.