Phosphorolysis of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and other 5-substituted-2'-deoxyuridines by purified human thymidine phosphorylase and intact blood platelets.
Various 5-substituted-2'-deoxyuridines (dUrd), including 5-ethyl,5-propyl-, 5-trifluoromethyl-, 5-hydroxymethyl-, 5-formyl-, 5-vinyl-, (E)-5-(2-chlorovinyl)-, (E)-5-(2-bromovinyl)-, 5-fluoro-, 5-chloro-, 5-bromo-, 5-iodo-, 5-cyano-, 5-thiocyano-, 5-nitro- and 5-amino-dUrd, were shown to be effective substrates for the thymidine (dThd) phosphorylase isolated from human blood platelets. Some of dUrd analogs, i.e. the highly potent and selective antiherpes agent (E)-5-(2-bromovinyl)-dUrd, were degraded more rapidly than the natural substrates, dUrd and dThd. All dUrd analogs were also readily catabolised by intact human blood platelets. The potent inhibitors of thymidine phosphorylase, 6-amino-thymine and 6-amino-5-bromo-uracil, strongly inhibited the phosphorolysis of (E)-5-(2-bromovinyl)-dUrd by both purified enzyme and intact platelets.
D001792:Blood Platelets / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D001976:Bromouracil / Q000031:analogs & derivatives / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010430:Pentosyltransferases / Q000378:metabolism*; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D013941:Thymine / Q000031:analogs & derivatives / Q000494:pharmacology
C006562:6-aminothymine; C020235:brivudine; D001976:Bromouracil; C039893:6-amino-5-bromouracil; D010430:Pentosyltransferases; D013939:Thymidine Phosphorylase; D001973:Bromodeoxyuridine; D013941:Thymine; D003857:Deoxyuridine