Uridine phosphorylase 효소의 강력한 억제제로 개발된 유리딘 비고리핵산들(Benzylacyclouridine: BAU, HM-BAU, suc-BAU, BBAU, HM-BBAU, suc-BBAU, and BBBAU)이 uridine,의 사람 적혈구 내로의 수송(Zero-trans influx)에 미치는 영향에 관하여 rapid sampling technique을 이용하여 고찰하였다. 이 실헙에서 유리딘-비고리핵산들은 parent compounds인 BAU, BBAU와 같이 uridine 수송에 상경적인 억제작용을 보였다. 그러나 suc-BBAU와 BBBAU는 비상경적인 억제요소도 나타냈다. Uridine 수송억제제로서 효력의 크기는 BBAU ~ HM-BBAU ~ suc-BBAU>BAU ~ suc-BAU ~ HM-BAU이었으며, 그 억제상수는 각각 19, 23, 38, 112, 124, 174 그리고 176μM이었다. 본 실험 결과에서는 uridine 수송에 있어서 BAU의 C5 자리의 친지방성 치환 group의 크기에 따라 억제효력이 다른 것이 시사되었다.
Various Benzylacyclouridine (BAU, HM-BAU, suc-BAU, BBAU, HMBBAU, suc-BBAU, and BBBAU) developed as specifc inhibitors of uridine phosphorylase (UrdPase), inhibit transport (zero-trans influx) of ridine (Urd) in human erythrocytes. The inhibition pattern of these compounds is competitive, though suc-BBAU and BBBAU show a slight noncompetivieness. The order of potency as an inhibitor of the nucleoside transport system is BBAU ~ HM-BBAU ~ suc-BBAU > BBBAU > BAU ~ suc-BAU ~ HM-BAU (K_1 values of 19, 23, 38, 112, 124, 174 and 176 μM, respectively). These data indicate that there is a differnece in potency of Urd transport inhibition between the analogs of BAU and BBAU. Further, the potency correlates with the hydrophobicity of the compound, but it has a limit in the size of C5 substitution. Abbreviation: BAU (5-benzylacyclouridine), 5-benzyl-1-(2 -hydroxyethoxymethyl) uracil; HM-BAU (3 -hydroxymethyl-BAU), 5-benzyl-1- [(1 ,3 -dihydroxy-2-propoxy) methyl]uracil; suc-BAU, 3 -succinyl-BAU; BBAU (benzyloxybenzylacyclouridine), 5-( m-benzyloxybenByl)-1-(2 -hydroxyethoxymethyl)uracil; HM-BBAU (3 -hydroxymethyl-BBAU), 5-(m-benzyloxybenzyl)-1- [(1 3 -dihyd.oxy-2-p.epoxy)methyll u.acil; suc-BAU, 3 -succinyl-BBAU; BBBAU, 5- f 3-(4-benzyloxyben-Eyl)benzyll -1-(2 -hydroxyethoxymethyl)uracil; Urdpase, uridine phosphorylase; Urd, Uridine; Fd-Urd, 5-fluoro-2 -deoxyuridine; AcThd, aoyclothyrnidine; AcUrd, acyclouridine; dThd, thymidine; NBMPR, nitrobenzylthioisone; FUra, 5-fluorouracil.
