How a sugar unit is defined? I am trying to understand the structure of calicheamicins, and it is noted that They consist of an enediyne headpiece and a modified carbohydrate tail consisting of four sugar units and an unusually substituted aromatic ring. I can understand in the picture where sugar unit is referred, but I would like a general definition. Thank you

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    $\begingroup$ The sugar unit features a linear chain of carbon carbon bonds. Distinct units are usually connected by glycosidic bonds (which may be hydrolyzed without breaking carbon carbon bonds). $\endgroup$ – Karsten Theis May 11 at 11:36
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    $\begingroup$ A sugar unit is a monosaccharide, the Wikipedia entry is a good introduction en.wikipedia.org/wiki/Monosaccharide $\endgroup$ – Waylander May 11 at 13:53

Calicheamicins are natural products, which were isolated from the fermentation broth of Micromonospora echinospora subsp. calichensis. These antibiotics exhibited significant activity against Gram-positive and Gram-negative bacteria in vitro. Calicheamicin $\gamma_1$ (Ref.1) demonstrated antitumor activity against P388 leukemia and B16 melanoma in vitro (Ref.2).

The structure of Calicheamicin $\gamma_1$ contains biologically active part of bicycloring system, which is described in the following diagram:

The Structure of Calicheamicin g1

The rest of the structure contains four modified sugar units and one aromatic nucleus. The sugar 1 unit is a 6-deoxy-4-aminohexose unit (that's why it is called a modified sugar). Its anomeric oxygen (hemiacetyl $\ce{OH}$) bound to the $\ce{C}$9 position of the endiyne unit in $\beta$-linkage. The sugar 2 unit is a 2,6-dideoxy-4-thiohexose unit, hence it is also a modified sugar. This linkage is unusual among other sugar linkages in natural origin. The inkage is a hydroxyl amine bond ($\ce{-NH-O-}$) without eliminating $\beta$-$\ce{OH}$ of 2nd sugar unit. According to proposed biosynthetic pathway, these two sugars have been added to endiyne unit in first and second steps of the pathway:

The Biosynthetic Path of Calicheamicin

The third step of the biosynthesis is addition of the aromatic nucleus (5-iodo-4-hydroxy-2,3-methoxy-6-methylbenzoate unit) to 4-thial group of sugar 2 as a thioester bond. The forth and fifth additions of other sugar units can be alternative. Nonetheless, one sugar (a 6-deoxy-3-O-methylhexose unit) attached to the free 4-phenolic $\ce{OH}$ group of aromatic nucleus in $\alpha$-linkage. The last sugar unit is attached with its $\alpha$-$\ce{OH}$ of the anomeric center to the free 2-$\ce{OH}$ group of the first sugar in $2 \rightarrow 1$ linkage. The unusual about this sugar is it is a pentose (a 2-deoxy-3-O-methyl-4-N-ethylaninopentose unit) instead of hexose among other three.

You can find a good description of mechanism of action of Calicheamicin $\gamma_1$ in Ref.3.

I hope this is what you want to know about this molecule.


  1. May D. Lee, Theresa S. Dunne, Marshall M. Siegel, Conway C. Chang, George O. Morton, Donald B. Borders, “Calichemicins, a Novel Family of Antitumor Antibiotics. 1. Chemistry and Partial Structure of Calichemicin $\gamma_1$,” J. Am. Chem. Soc. 1987, 109(11), 3464-3466 (https://doi.org/10.1021/ja00245a050).
  2. W. M. Maiese, M. P. Lechevalier, H. A. Lechevalier, J. Korshalla, N. Kuck, A.Fantini, M.J. Wildey, J. Thomas, M. Greenstein, “Calicheamicins, a novel family of antitumor antibiotics: taxonomy, fermentation and biological properties,” The Journal of Antibiotics 1989, 42(4), 558-563 (DOI: 10.7164/antibiotics.42.558).
  3. Miklós Simonyi, ”The Concept of Chiral Conformers and its Significance in Molecular Pharmacology,” In Advances in Drug Research: Volume 30; Bernard Testa, Urs A. Meyer, Eds.; Academic Press: San Diego, CA, 1997, pp. 73-111 (ISBN: 0-12-013330-X).
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    $\begingroup$ thank you!may I aks if you have such a clear explanation about the agent N-acetyl gamma calicheamicin dimethyl hydrazide (NAc-gamma calicheamicin DMH) as well? $\endgroup$ – marilu May 12 at 9:35
  • $\begingroup$ Sounds like it it is calicheamicin $\gamma_1$ with a linker. I didn't know biochemical manipulation of the natural product. Yet, it won't hurt if you ask the question. $\endgroup$ – Mathew Mahindaratne May 12 at 9:41
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    $\begingroup$ yes it has been used for the production of a drug, gemtuzumab ozogamicin. thank you! ema.europa.eu/en/documents/assessment-report/… $\endgroup$ – marilu May 12 at 9:44
  • $\begingroup$ hello! could someone help me to decipher the structure of this molecule? I am trying to understand the structure of gemtuzumab ozogamicin: The anti-CD33 antibody is acylated with the bifunctional AcBut linker, which allows for hydrazone formation with the calicheamicin derivative. This derivative, N-acetyl-gcalicheamicin dimethylhydrazide (DMH), has a disulfide stabilized by both the two methyl groups and the calicheamicin bicyclic core, and an acetylated amino sugar. References: Joel C. Barrish, Percy H. Carter, Peter T. W. Cheng, Robert Zahler Accou... $\endgroup$ – marilu May 15 at 20:37
  • $\begingroup$ @ marilu: You should post this as a new question for better results. $\endgroup$ – Mathew Mahindaratne May 16 at 2:01

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