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Inaccurate Serelaxin Chemical Structure
To the Editor:
I would like to comment on what appears to be an error in the October 2013 issue of P&T in the Drug Forecast article, entitled “Serelaxin, a ‘Breakthrough’ Investigational Intravenous Agent for Acute Heart Failure” (Volume 10, pages 606–611).
My concern has to do with the legend of Figure 1, “Structural formula of serelaxin. Available at:
Serelaxin is correctly referred to in the text as a recombinant form of human relaxin-2, a naturally occurring polypeptide, with a molecular formula of C256H408N74O74S8 (molecular weight: 5.96 kilodaltons or 5,960 g/mol). A more descriptive structural formula can be found at
Investigation of the structural formula section of the AMA reference (as well as others) reveals that serelaxin is an insulin-like peptide with a total of 65 amino acids forming an A and B chain with three disulfide bridges. Furthermore, one of the amino acids present in the sequence of serelaxin is that of
Of all the amino acids in serelaxin, this particular amino acid is singled out in the AMA’s reference in the ‘structural formula’ section (just below the complete listing of the primary amino acid sequences for both the A and B chains of serelaxin) because it is a “modified residue.”
Because lengthy peptide sequences are typically listed in standard single-letter amino acid code, the authors might have chosen to include the chemical structure of
If a reader has simply adopted a “pictures and graphs”–only approach when reading this article, as many busy health professionals and scientists are prone to do, and if reading the main text of the article is avoided, Figure 1, as presented, may imply that serelaxin is a small-molecule drug, when in fact it is a considerably larger peptide drug. Peptides can differ greatly in terms of their oral bio-availability, compared with small-molecule drugs, in large part because of the presence of acid-sensitive peptide (amide) bonds. Such bonds are generally readily hydrolyzed at low pH in the stomach, thus destroying a peptide’s molecular structure and, hence, its biological action.
As the article states, serelaxin is administered intravenously, probably as a means to avoid this issue. Furthermore, a quick online search reveals that
In closing, while this chemical misrepresentation is likely a simple oversight and one that will probably not change any practitioner’s mind about serelaxin, it highlights the need for pharmacists to be mindful of accurately representing the structural and chemical properties of drug molecules.
Associate Professor of Pharmaceutical Sciences–Medicinal Chemistry
Gregory School of Pharmacy
Palm Beach Atlantic University
West Palm Beach, Florida