Inhibition of hemoglobin S polymerization by N-terminal band 3 peptides: new class of inhibitors: solubility studies.
Inhibition of hemoglobin S polymerization by N-terminal band 3 peptides: new class of inhibitors: solubility studies.
复制标题
N 端带 3 肽对血红蛋白 S 聚合的抑制：新型抑制剂：溶解度研究。
DOI：
10.1002/ajh.2830470208
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发表时间：
1994
影响因子：
12.8
通讯作者：
Harris,JW
中科院分区：
文献类型：
--
作者：
Danish,EH;Lundgren,DW;Harris,JW
设计了对应于条带3的N末端氨基酸（AA）的两种合成肽，以通过两种不同的机制抑制脱氧血红蛋白S（脱氧S）聚合。肽I是一种N：1- 15 AA片段，用于结合单个脱氧S分子的2，3-二磷酸甘油酸（2，3-DPG）受体基因座，其中5-7个AA向内延伸，其余10 - 8个AA突出到血红蛋白（Hb）S外部，从而通过空间位阻抑制聚合。肽II由两个N：1 - 8AA + K（赖氨酸）序列组成，通过赖氨酸由偶联剂连接，并用于结合两个脱氧S分子的2，3-DPG位点，将它们拴在一起形成不能进入聚合物链的“二元血红蛋白复合物”。脱氧S的有效浓度降低会导致聚合减少。随着肽浓度的增加，血红蛋白氧结合曲线逐渐发生红移，从而证明肽与2，3-DPG受体位点的结合。脱氧S聚合的抑制作用通过测量纯化的、剥离的Hb S溶液的平衡溶解度来研究。这两种肽均表现出生理学显著的抑制作用，肽II在1：1肽：Hb S比例下实现了溶解度的接近最大增加。© 1994 Wiley利斯公司
Two synthetic peptides corresponding to the N‐terminal amino acids (AA) of band 3 were designed to inhibit deoxyhemoglobin S (deoxy S) polymerization through two different mechanisms. Peptide I, an N:1–15AA fragment, was employed to bind to the 2,3‐diphosphoglycerate (2,3‐DPG) receptor locus of single deoxy S molecules with 5–7 AA extending internally and the remaining 10‐8 AA projecting external to hemoglobin (Hb) S, thereby inhibiting polymerization by steric hindrance. Peptide II consisted of two N:1‐8AA + K (lysine) sequences linked by a coupler through the lysine, and it was employed to bind to the 2,3‐DPG loci oftwodeoxy S molecules, tethering them together to form “binary hemoglobin complexes” incapable of entering the polymer chains. Decreased polymerization would result from reduction in effective concentration of deoxy S.Binding of peptides to the 2,3‐DPG receptor loci was demonstrated by a progressive rightward shift in the hemoglobin oxygen binding curves as a function of increasing peptide concentrations.Inhibition of deoxy S polymerization was studied by equilibrium solubility measurements of purified, stripped solutions of Hb S. Physiologically significant inhibition was demonstrated for both peptides with near‐maximum increases in solubility achieved by Peptide II at 1:1 peptide:Hb S ratios.These peptides represent a new class of inhibitors of deoxy S polymerization. © 1994 Wiley‐Liss, Inc.