| Revision as of 23:17, 7 August 2011 editCheMoBot (talk | contribs)Bots141,565 edits Updating {{chembox}} (no changed fields - added verified revid - updated 'DrugBank_Ref', 'UNII_Ref', 'ChEMBL_Ref', 'ChEBI_Ref', 'KEGG_Ref') per Chem/Drugbox validation (report [[Wikipedia_talk:Wi← Previous edit |
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{{chembox |
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{{chembox |
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| verifiedrevid = 443583603 |
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| verifiedrevid = 443585061 |
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|ImageFile=Desosamine.png |
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| ImageFile=Desosamine.png |
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|ImageSize=200px |
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| ImageSize=200px |
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| IUPACName=3,4,6-Trideoxy-3-(dimethylamino)-<small>D</small>-''xylo''-hexose |
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|IUPACName=(2''R'',3''S'',5''R'')-3-Dimethylamino-2,5-dihydroxyhexanal |
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| SystematicName=(2''R'',3''S'',5''R'')-3-(Dimethylamino)-2,5-dihydroxyhexanal |
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|OtherNames= |
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| OtherNames= |
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|Section1= {{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| CASNo_Ref = {{cascite|correct|??}} |
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| CASNo=5779-39-5 |
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| Beilstein = 2412240 |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 32540 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 147813 |
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| ChemSpiderID = 147813 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 3NR0662443 |
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| PubChem=168997 |
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| 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 |
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| 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 |
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| InChIKey = VTJCSBJRQLZNHE-CSMHCCOUBT |
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| InChIKey = VTJCSBJRQLZNHE-CSMHCCOUBT |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| 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 |
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| 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 |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = VTJCSBJRQLZNHE-CSMHCCOUSA-N |
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| StdInChIKey = VTJCSBJRQLZNHE-CSMHCCOUSA-N |
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| CASNo=5779-39-5 |
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| PubChem=168997 |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 32540 |
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| SMILES = O=C(O)(N(C)C)C(O)C |
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| SMILES = O=C(O)(N(C)C)C(O)C |
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|Section2= {{Chembox Properties |
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|Section2={{Chembox Properties |
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| Formula=C<sub>8</sub>H<sub>17</sub>NO<sub>3</sub> |
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| Formula=C<sub>8</sub>H<sub>17</sub>NO<sub>3</sub> |
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| MolarMass=175.23 g/mol |
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| MolarMass=175.23 g/mol |
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| Appearance= |
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| Density= |
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|Section3= {{Chembox Hazards |
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|Section3={{Chembox Hazards |
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| MainHazards= |
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| FlashPt= |
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| AutoignitionPt = |
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}} |
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'''Desosamine''' is a 3-(dimethylamino)-3,4,6-trideoxyhexose found in certain ] such as the commonly prescribed ].<ref name="Rodriguez">{{cite journal |author=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 (Reading, Engl.) |volume=152 |issue=Pt 3 |pages=667–73 |year=2006 |month=March |pmid=16514147 |doi=10.1099/mic.0.28680-0 }}</ref><ref name="Flickenger">{{cite journal |author=Flickinger MC, Perlman D |title=Microbial degradation of erythromycins A and B |journal=J. Antibiot. |volume=28 |issue=4 |pages=307–11 |year=1975 |month=April |pmid=1150530 |url=http://www.journalarchive.jst.go.jp/jnlpdf.php?cdjournal=antibiotics1968&cdvol=28&noissue=4&startpage=307&lang=en&from=jnlabstract }}</ref> |
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'''Desosamine''' is a 3-(dimethylamino)-3,4,6-trideoxyhexose found in certain ] (contain a high level of microbial resistance) such as the commonly prescribed ],<ref name="Rodriguez">{{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 }}</ref><ref name="Flickinger">{{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 }}</ref> ], ], methymycin, narbomycin, ], ] and ]. 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.<ref>{{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 }}</ref> The biological action of the desosamine-based macrolide antibiotics is to inhibit the bacterial ribosomal protein synthesis.<ref>{{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 }}</ref> These antibiotics which contain desosamine are widely used to cure bacterial-causing infections in human respiratory system, skin, muscle tissues, and urethra. |
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==Biosynthesis== |
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== Discovery == |
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Although desosamine has been found in many macrolide antibiotics, the complete chemical structure of desosamine was not determined until 1962.<ref name=":0" /> ] 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.<ref name=":0">{{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 }}</ref> |
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==Biosynthesis == |
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Six ]s are required for its biosynthesis from ] in ''Streptomyces venezuelae''.<ref name="Rodriguez" /> |
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Six ]s are required for desosamine biosynthesis from ] in ''Streptomyces venezuelae''.<ref name="Rodriguez" /><ref>{{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 }}</ref> 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. <ref>{{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 }}</ref> |
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==References== |
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{{reflist}} |
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== Degradation == |
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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.<ref>{{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}}</ref> 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.<ref>{{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}}</ref> |
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== Drug resistance == |
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{{biochem-stub}} |
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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.<ref>{{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 }}</ref> |
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{{organic-compound-stub}} |
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== See also == |
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* ] |
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== References == |
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{{reflist|30em}} |
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== External links == |
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