Chem167_L18_Jun4_final

Cofactor cofactor is crucial to pyrimidine and dna

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Unformatted text preview: to ac#ve sulfonamide • Acts as a prodrug • Sulfanilamide - first synthe#c an#bacterial agent ac#ng on a wide range of infec#ons Sulfanilamides - applica#ons Notes • An#bacterial drugs of choice prior to penicillins (1930s) • Superseded by penicillins Current uses • Treatment of urinary tract infec#ons • Eye lo#ons • Treatment of gut infec#ons • Treatment of mucous membrane infec#ons Target enzyme • Dihydropteroate synthetase - bacterial enzyme • Not present in human cells • Important in the biosynthesis of the tetrahydrofolate cofactor • Cofactor is crucial to pyrimidine and DNA biosynthesis • Crucial to cell growth and division Sulfonamide Mechanism of ac#on Binding interac#ons 2N H" " " H-Bond" van der Waals" interactions" Ionic bond" O" C" O" Active site" Normal substrate PABA H2" " "N O" S" O" NR" " Active site" sulfonamide Metabolic differences between bacterial and mammalian cells Dihydropteroate synthetase is present only in bacterial cells (selec#vity) Transport protein for folic acid is only present in mammalian cells (selec#vity) Can require resistance by producing more PABA (compe##ve inhibitor) Examples of Sulfonamides Sulfadoxine O H2N S O N HN N MeO OMe • Belongs to a new genera#on of sulfonamides • Long las#ng an#bacterial agent • Once weekly dosing regime • Sulfadoxine + pyrimethamine = Fanisdar • Used for the treatment of malaria H3C N NH 2 N Cl NH 2 Pyrimethamine 1. Cell Wall Biosynthesis β- Lactams Growing cell wall . . . . . . . ...... .. .. .. . . .. . . .. . .. . . . . . . ........ . Vancomycin Cross- linking Bacitracin Cell membrane Cytoplasm . . . . Transglycosida*on Gly NAG Carrier lipid L- Ala D- Glu L- Lys NAM L- Ala Amino acid D- Ala Cycloserine D- Ala- D- Ala • Building block par*all...
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This note was uploaded on 01/15/2014 for the course CHEM 167 taught by Professor Amaro during the Winter '13 term at UCSD.

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