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Chemical
Properties of Zadaxin
Zadaxin (thymalfasin), originally isolated as a natural substance
from thymus tissue, is a pure, synthetic amino-terminal acylated
peptide of 28 amino acids (molecular weight 3108; Figure 1).
Some early studies utilized a partially purified thymic preparation
(thymic fraction 5 or TF5) that contained about 1% thymalfasin;
(1,2) however, most studies have
utilized synthetic preparations of Zadaxin made by solid phase
peptide synthesis. (3) |
Figure 1.
Primary structure of thymalfasin |
Endogenous thymalfasin can be detected in serum, where levels
measured in healthy adults by immunoassays are in the 0.1 to
1 ng/mL range. (4-7) The circulating
concentration of thymalfasin tends to be lower in diseased individuals
and higher during pregnancy. (8-11)
The source and mechanisms of release and regulation of circulating
thymalfasin are unknown. Thymalfasin is contained in the sequence
of prothymosin, a 126-amino-acid peptide that is found in the
cell nucleus (12-16), and that
has been examined in terms of potential effects on cell proliferation.
(17-19) Thymalfasin, found in highest concentrations
in the thymus, has also been found in spleen, lung, kidney,
brain, blood, and a number of other tissues. Thymalfasin has
amino-acid sequence homology with interferon alpha (IFNα)
and members of the glucagon-vasoactive intestinal peptide (VIP)-secretin
family of peptides. Although binding of high concentrations
of thymalfasin to VIP receptors has been reported
(20,21) and thymalfasin has been found to weakly stimulate
adenylate cyclase activity, the receptors for thymalfasin are
not known. It is possible that thymalfasin has intracellular
receptors, as it can fold into a structured helix in organic
solvents and thus may cross the membrane unassisted.
(22) |
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