desosamine
{{chembox
| verifiedrevid = 443585061
| ImageFile=Desosamine.png
| ImageSize=200px
| IUPACName=3,4,6-Trideoxy-3-(dimethylamino)-D-xylo-hexose
| SystematicName=(2R,3S,5R)-3-(Dimethylamino)-2,5-dihydroxyhexanal
| OtherNames=
|Section1={{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|??}}
| CASNo=5779-39-5
| Beilstein = 2412240
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 32540
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 147813
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 3NR0662443
| PubChem=168997
| InChI = 1/C8H17NO3/c1-6(11)4-7(9(2)3)8(12)5-10/h5-8,11-12H,4H2,1-3H3/t6-,7+,8+/m1/s1
| InChIKey = VTJCSBJRQLZNHE-CSMHCCOUBT
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI=1S/C8H17NO3/c1-6(11)4-7(9(2)3)8(12)5-10/h5-8,11-12H,4H2,1-3H3/t6-,7+,8+/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = VTJCSBJRQLZNHE-CSMHCCOUSA-N
| SMILES = O=C[C@H](O)[C@@H](N(C)C)C[C@H](O)C
}}
|Section2={{Chembox Properties
| Formula=C8H17NO3
| MolarMass=175.23 g/mol
| Appearance=
| Density=
| MeltingPt=
| BoilingPt=
| Solubility=
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|Section3={{Chembox Hazards
| MainHazards=
| FlashPt=
| AutoignitionPt =
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Desosamine is a 3-(dimethylamino)-3,4,6-trideoxyhexose found in certain macrolide antibiotics (contain a high level of microbial resistance) such as the commonly prescribed erythromycin,{{cite journal | vauthors = Rodríguez E, Peirú S, Carney JR, Gramajo H | title = In vivo characterization of the dTDP-D-desosamine pathway of the megalomicin gene cluster from Micromonospora megalomicea | journal = Microbiology | volume = 152 | issue = Pt 3 | pages = 667–673 | date = March 2006 | pmid = 16514147 | doi = 10.1099/mic.0.28680-0 | doi-access = free }}{{cite journal | vauthors = Flickinger MC, Perlman D | title = Microbial degradation of erythromycins A and B | journal = The Journal of Antibiotics | volume = 28 | issue = 4 | pages = 307–11 | date = April 1975 | pmid = 1150530 | doi = 10.7164/antibiotics.28.307 | doi-access = free }} azithromycin, clarithromycin, methymycin, narbomycin, oleandomycin, picromycin and roxithromycin. As the name suggests, these macrolide antibiotics contain a macrolide or lactone ring and they are attached to the ring desosamine which is crucial for bactericidal activity.{{cite journal | vauthors = Burgie ES, Holden HM | title = Molecular architecture of DesI: a key enzyme in the biosynthesis of desosamine | journal = Biochemistry | volume = 46 | issue = 31 | pages = 8999–9006 | date = August 2007 | pmid = 17630700 | pmc = 2528198 | doi = 10.1021/bi700751d }} The biological action of the desosamine-based macrolide antibiotics is to inhibit the bacterial ribosomal protein synthesis.{{cite journal | vauthors = Vázquez-Laslop N, Mankin AS | title = How Macrolide Antibiotics Work | journal = Trends in Biochemical Sciences | volume = 43 | issue = 9 | pages = 668–684 | date = September 2018 | pmid = 30054232 | pmc = 6108949 | doi = 10.1016/j.tibs.2018.06.011 }} These antibiotics which contain desosamine are widely used to cure bacterial infections in human respiratory system, skin, muscle tissues, and urethra.
Discovery
Although desosamine has been found in many macrolide antibiotics, the complete chemical structure of desosamine was not determined until 1962. Nuclear magnetic resonance spectroscopy data was used to establish the complete configuration of desosamine. The hydrogen atoms at the C1,C2,C3, and C5 positions are all found to be axial.{{Cite journal | vauthors = Woo PW, Dion HW, Durham L, Mosher HS |date= January 1962 |title=The stereochemistry of desosamine, an nmr analysis |journal=Tetrahedron Letters|language=en|volume=3|issue=17|pages=735–739|doi=10.1016/S0040-4039(00)70510-7 }}
Biosynthesis
Six enzymes are required for desosamine biosynthesis from TDP-glucose in Streptomyces venezuelae.{{cite journal | vauthors = Burgie ES, Holden HM | title = Molecular architecture of DesI: a key enzyme in the biosynthesis of desosamine | journal = Biochemistry | volume = 46 | issue = 31 | pages = 8999–9006 | date = August 2007 | pmid = 17630700 | pmc = 2528198 | doi = 10.1021/bi700751d }} In addition to the required enzymes, there are eight important open reading frames known as the des regions, they are desI~desVIII, these eight frames are the necessary genes used in desosamine biosynthesis, among the 8 des regions, the desI gene implements C-4 deoxygenation by the enzymatic activity of dehydrase. {{cite journal | vauthors = Borisova SA, Zhao L, Sherman DH, Liu HW | title = Biosynthesis of desosamine: construction of a new macrolide carrying a genetically designed sugar moiety | journal = Organic Letters | volume = 1 | issue = 1 | pages = 133–6 | date = July 1999 | pmid = 10822548 | doi = 10.1021/ol9906007 }}
Degradation
Degradation of several of the aforementioned antibiotics yields the desosamine sugar. It is found in combination with the smaller macrolide rings, always attached at C-3 or C-5 of the aglycone. Alkaline degradation found the sugar to be a D-hexose derivative.{{cite journal | vauthors = Bolton CH, Foster AB, Stacey M, Webber JM |date=1961 |title=Carbohydrate components of antibiotics. Part I. Degradation of desosamine by alkali: Its absolute configuration at position 5 |journal=Journal of the Chemical Society |volume=1961 |issue=4 |pages=4831–4836 |doi=10.1039/JR9610004831}} Glycosidic cleavage of methomycin produces aglycone methynolide and the basic sugar desosamine, whose structure had been determined by oxidative degradation to crotonaldehyde and by other experiments.{{cite journal | vauthors = Berry M |date=1963 |title=The macrolide antibiotics |journal=Quarterly Reviews, Chemical Society |volume=17 |issue=4 |pages=343–361 |doi=10.1039/QR9631700343}}
Drug resistance
Macrolide antibiotics that contain desosamine as an amino sugar in their chemical structures sometimes encounter drug-resistant bacteria. The target-site modification can result in changing chemical structure of the antibiotics, for example, a methylation mutation, which will block the drug from normally functioning.{{cite journal | vauthors = Klugman KP, Lonks JR | title = Hidden epidemic of macrolide-resistant pneumococci | language = en-us | journal = Emerging Infectious Diseases | volume = 11 | issue = 6 | pages = 802–7 | date = June 2005 | pmid = 15963272 | pmc = 3367596 | doi = 10.3201/eid1106.050147 }}
See also
References
{{reflist|30em}}
External links
- [https://www.ncbi.nlm.nih.gov/mesh/67110125 Desosamine in the US National Library of Medicine MeSH (Medical Subject Headings):]
- [https://meshb.nlm.nih.gov/record/ui?name=Deoxy%20Sugars Deoxy Sugar in the US National Library of Medicine MeSH (Medical Subject Headings)]