# What is "dithreitol"?

The article by Hu et al. [1] mentions a compound "dithreitol" in the Saliva Proteome Analysis section (emphasis mine):

For the "shotgun" approach, saliva samples (1 mL) were pre-fractionated with the use of Millipore ultracentrifuge filters (Millipore Corp., Billerica, MA, USA). Individual fractions were treated with 10 mM dithreitol for 30 min and then 50 mM iodoacetamide for 30 min.

PubChem doesn't reveal any details as to what this compound exactly is and suggests alternative spelling, e.g. D-threitol.

Google Books search results in several mentions of this compound in the literature, but I didn't find any further details except that it's probably a sulfhydryl reagent. This makes me think that "dithreitol" could be another name for dithiothreitol, but I didn't manage to find any solid references to support this proposition.

To sum it up: what is dithreitol, exactly, and what chemical and structural formulas does it posses?

### References

1. Hu, S.; Li, Y.; Wang, J.; Xie, Y.; Tjon, K.; Wolinsky, L.; Loo, R. R. O.; Loo, J. A.; Wong, D. T. Human Saliva Proteome and Transcriptome. J Dent Res 2006, 85 (12), 1129–1133. DOI: 10.1177/154405910608501212.
• In some papers, like this pubmed.ncbi.nlm.nih.gov/3139612, are mentioned urea-dithreitol-sodium lauryl sulphate (UDS) and urea-dithiothreitol (UDT). If you google "uds urea lauryl", you get many results which define UDS as the ingredients above plus dithiothreitol. So I guess that is just a kinky name for dithiothreitol. Mar 20 '20 at 10:20
• @The_Vinz If you found an article that explicitly states that dithreitol≡dithiothreitol, please feel free to post an answer. Mar 20 '20 at 10:22
• @andselisk, It is most likely a spelling mistake which is not uncommon. If SciFinder does not list it (as written) then it is not a standard name. I got zero results. Mar 20 '20 at 13:15
• @andselisk, Could you locate the original method of the procedure used by the authors? It is a chain mistake and other people blindly quoted the same name for dithiothreitol. The same thing happens for references. Believe it or not there are so many (mostly minor) mistakes in the published works that one cannot imagine. My boss used to say "Paper never refused an ink"...meaning you can write whatever you want, the paper won't say anything. Mar 20 '20 at 13:45
• DTT is very commonly used. It is interesting that the (puported) error arises so often, but some typos should not seem entirely strange, given the frequency with which DTT is reported used, the ease with which the typo can be committed, and the ease with which it could be overlooked or ignored as insignificant. Mar 20 '20 at 16:33

For the "shotgun" approach, saliva samples ($$\pu{1 mL}$$) were pre-fractionated with the use of Millipore ultracentrifuge filters (Millipore Corp., Billerica, MA, USA). Individual fractions were treated with $$\pu{10 mM}$$ dithreitol for $$\pu{30 min}$$, and then $$\pu{50 mM}$$ iodoacetamide for $$\pu{30 min}$$.

This reaction sequence in Ref.1 has a clear intention: First, break disulfide bonds in saliva proteins using a thiol exchanging reagent and then trap the recently formed thiol groups by iodoacetamide (Ref.2). According to Ref.2:

Alkylation of cysteine thiols with iodo, bromo or chloro substituted acetic acid or acetamide is a classic approach that has been exploited since the 1930′s.

Thus, it is safe to assume that this second reaction is intended to trap thiol group as quickly as possible (The relative reaction rates between glutathione and these halogenated acetates are $$100:60:1$$ for iodo-, bromo- and chloro-acetates respectively; Ref.3).

Also keep in mind that disulfide reduction to corresponding thiol is accomplished primarily by thiol exchange type reagents such as dithiothreitol (DTT) or 2-mercaptoethanol (ME). Thus, it is also safe to assume that dithreitol mentioned in Ref.1 is definitely a thiol exchanging reagent, possibly DTT. Therefore, I think it is a chain mistake as M. Farooq suggested in his comment.

References:

1. S. Hu, Y. Li, J. Wang, Y. Xie, K. Tjon, L. Wolinsky, R. R. O. Loo, J. A. Loo, D. T. Wong, "Human Saliva Proteome and Transcriptome," J. Dent. Res. 2006, 85(12), 1129–1133 (DOI: 10.1177/154405910608501212).
2. Jakob R. Winther, Colin Thorpe, "Quantification of Thiols and Disulfides," Biochimica et Biophysica Acta 2014, 1840(2), 838-846 (https://doi.org/10.1016/j.bbagen.2013.03.031).
3. Frank Dickens, "CLII. Interaction of halogenacetates and SH compounds. The reaction of halogenacetic acids with glutathione and cysteine. The mechanism of iodoacetate poisoning of glyoxalase," Biochem J. 1933, 27(4), 1141–1151 (doi: 10.1042/bj0271141).
• One of the publication in andselisk's search even had the CAS number, "dithreitol, 3483-12-3". Another publication had "dithio dithreitol". Many publications have something like "dithreitol (DTT)". It reminds me of mis-citations of nature.com/articles/227680a0. Mar 22 '20 at 3:10