SUBSTITUTED BENZALDEHYDES DESIGNED TO INCREASE THE OXYGEN-AFFINITY OF HUMAN-HEMOGLOBIN AND INHIBIT THE SICKLING OF SICKLE ERYTHROCYTES
SUBSTITUTED BENZALDEHYDES DESIGNED TO INCREASE THE OXYGEN-AFFINITY OF HUMAN-HEMOGLOBIN AND INHIBIT THE SICKLING OF SICKLE ERYTHROCYTES
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DOI：
10.1111/j.1476-5381.1984.tb10775.x
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发表时间：
1984-01-01
影响因子：
7.3
通讯作者：
WOOTTON, R
中科院分区：
文献类型：
--
作者：
BEDDELL, CR;GOODFORD, PJ;WOOTTON, R
取代的苯甲醛[2“-甲酰基-4-联苯乙酸、5-（2-甲酰基苯氧基）戊酸和5-（2-甲酰基-3-羟基苯氧基）戊酸]被设计为在α-甲基-β-氨基末端残基之间的位点优先结合人Hb的氧构象。亚单位。这些化合物应该稳定Hb的氧化形式，从而增加其O2亲和力。该化合物产生了预期的效果，左移的O2饱和曲线的稀释血红蛋白溶液和全血，虽然结合到血红蛋白的模式是更复杂的设计假设比设想的。预测的最佳化合物也是一种有效的抑制剂，在低O2压力下，镰状细胞病纯合子患者的红细胞镰状化，并可能被证明是一种临床上有用的抗镰状化剂。
Substituted benzaldehydes [2''-formyl-4-biphenylacetic acid, 5-(2-formylphenoxy) pentanoic acid and 5-(2-formyl-3-hydroxyphenoxy) pentanoic acid] were designed to bind preferentially to the oxy conformation of human Hb at a site between the amino terminal residues of the .alpha.-subunits. Such compounds should stabilize the oxygenated form of Hb and thereby increase its O2 affinity. The compounds produced the expected effect, left-shifting the O2-saturation curve of dilute Hb solutions and of whole blood, although the binding pattern to Hb is more complex than envisaged by the design hypothesis. The predicted best compound is also a potent inhibitor, at low O2 pressure, of the sickling of erythrocytes from patients homozygous for sickle cell disease, and may prove to be a clinically useful anti-sickling agent.