Pseudouridimycin

Pseudouridimycin
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name (2S)-2-[[2-(diaminomethylideneamino)acetyl]-hydroxyamino]-N-[[(2R,3S,4R,5S)-5-(2,4-dioxo-1H-pyrimidin-5-yl)-3,4-dihydroxyoxolan-2-yl]methyl]pentanediamide;
CAS Number	1566586-52-4;
PubChem CID	72792467;
ChemSpider	59651398;
ChEBI	CHEBI:199549;
PDB ligand	PUM (PDBe, RCSB PDB);
Chemical and physical data
Formula	C17H26N8O9
Molar mass	486.442 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1=C(C(=O)NC(=O)N1)[C@H]2[C@@H]([C@@H]([C@H](O2)CNC(=O)[C@H](CCC(=O)N)N(C(=O)CN=C(N)N)O)O)O;
	InChI InChI=1S/C17H26N8O9/c18-9(26)2-1-7(25(33)10(27)5-22-16(19)20)15(31)21-4-8-11(28)12(29)13(34-8)6-3-23-17(32)24-14(6)30/h3,7-8,11-13,28-29,33H,1-2,4-5H2,(H2,18,26)(H,21,31)(H4,19,20,22)(H2,23,24,30,32)/t7-,8+,11+,12+,13-/m0/s1; Key:XDEYHXABZOKKDZ-YFKLLHAASA-N;

Pseudouridimycin (PUM) is an experimental antibiotic isolated from the soil bacteria Streptomyces albus. It inhibits bacterial RNA polymerase through a different mechanism from previously discovered drugs. Pseudouridimycin shows useful activity against pathogens such as multidrug-resistant Streptococcus pyogenes, and while it is unclear whether it will be suitable for development for medical use in its own right, modified derivatives have been produced with improved stability and similar antibiotic properties.^[1]^[2]^[3]^[4]^[5]

References

^ Chellat MF, Riedl R (October 2017). "Pseudouridimycin: The First Nucleoside Analogue That Selectively Inhibits Bacterial RNA Polymerase". Angewandte Chemie. 56 (43): 13184–13186. doi:10.1002/anie.201708133. PMID 28895263.
^ Maffioli SI, Sosio M, Ebright RH, Donadio S (March 2019). "Discovery, properties, and biosynthesis of pseudouridimycin, an antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase". Journal of Industrial Microbiology & Biotechnology. 46 (3–4): 335–343. doi:10.1007/s10295-018-2109-2. PMC 6405294. PMID 30465105.
^ Wang XK, Jia YM, Li YX, Yu CY (January 2022). "Total Synthesis of Pseudouridimycin". Organic Letters. 24 (2): 511–515. doi:10.1021/acs.orglett.1c03914. PMID 35005956.
^ Pavundurai Chandra K, Perumal D, Ragunathan P (February 2023). "Pseudouridimycin-A Potent Nucleoside Inhibitor of the RNA Polymerase Beta Prime Subunit of Streptococcus pyogenes". ACS Omega. 8 (8): 7989–8000. doi:10.1021/acsomega.2c07805. PMC 9979225. PMID 36873015.
^ Anwar AF, Cain CF, Garza MJ, Degen D, Ebright RH, Del Valle JR (January 2024). "Stabilizing Pseudouridimycin: Synthesis, RNA Polymerase Inhibitory Activity, and Antibacterial Activity of Dipeptide-Modified Analogues". ChemMedChem. 19 (1): e202300474. doi:10.1002/cmdc.202300474. PMC 10843019. PMID 37751316.

[1] Chellat MF, Riedl R (October 2017). "Pseudouridimycin: The First Nucleoside Analogue That Selectively Inhibits Bacterial RNA Polymerase". Angewandte Chemie. 56 (43): 13184–13186. doi:10.1002/anie.201708133. PMID 28895263.

[2] Maffioli SI, Sosio M, Ebright RH, Donadio S (March 2019). "Discovery, properties, and biosynthesis of pseudouridimycin, an antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase". Journal of Industrial Microbiology & Biotechnology. 46 (3–4): 335–343. doi:10.1007/s10295-018-2109-2. PMC 6405294. PMID 30465105.

[3] Wang XK, Jia YM, Li YX, Yu CY (January 2022). "Total Synthesis of Pseudouridimycin". Organic Letters. 24 (2): 511–515. doi:10.1021/acs.orglett.1c03914. PMID 35005956.

[4] Pavundurai Chandra K, Perumal D, Ragunathan P (February 2023). "Pseudouridimycin-A Potent Nucleoside Inhibitor of the RNA Polymerase Beta Prime Subunit of Streptococcus pyogenes". ACS Omega. 8 (8): 7989–8000. doi:10.1021/acsomega.2c07805. PMC 9979225. PMID 36873015.

[5] Anwar AF, Cain CF, Garza MJ, Degen D, Ebright RH, Del Valle JR (January 2024). "Stabilizing Pseudouridimycin: Synthesis, RNA Polymerase Inhibitory Activity, and Antibacterial Activity of Dipeptide-Modified Analogues". ChemMedChem. 19 (1): e202300474. doi:10.1002/cmdc.202300474. PMC 10843019. PMID 37751316.

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See also

References