Band 3 peptides inhibit deoxy S polymerization: viscosity studies.
Band 3 peptides inhibit deoxy S polymerization: viscosity studies.
复制标题
带 3 肽抑制脱氧 S 聚合：粘度研究。
DOI：
10.1002/ajh.2830420120
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发表时间：
1993
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
我们之前获得的证据表明，通过平衡溶解度测定，N端带3肽抑制脱氧血红蛋白S（脱氧S）聚合。一个N:1‐15AA片段结合到脱氧S的2,3‐二磷酸甘油酸（2,3‐DPG）受体位点上，有5 - 7个氨基酸（AA）在内部延伸，而10 - 8个氨基酸留在脱氧S的外部，并通过位阻抑制聚合。一个真正的镜像肽，对应于两个N:1‐8AA +赖氨酸(K)，通过偶联剂连接，与两个脱氧S分子的2,3‐DPG位点结合，将它们拴在一起形成不能进入聚合物链的“二元复合物”。可用于延伸链形成的脱氧S浓度的降低降低了聚合。我们现在报告了脱氧S纯化溶液的溶胶-凝胶转化的时间：粘度曲线，以及在平衡状态下凝胶固体性的研究。含有多肽的样品比类似脱氧S浓度的对照具有更长的滞后时间。镜像肽是比N:1‐15AA肽更有效的抑制剂。当镜像肽与血红蛋白摩尔比为0.25‐1:1时，滞后时间的增加相当于脱氧S浓度降低了15-25%，与预计的主要治疗效果相当。凝胶固体度由产率温度决定，与对照相比，镜像肽样品的凝胶固体度更低。这些结果支持了3带肽抑制脱氧S聚合的机制。©1993 Wiley‐Liss, Inc。
We have previously obtained evidence that N‐terminal band 3 peptides inhibited deoxyhemoglobin S (deoxy S) polymerization as determined by equilibrium solubility assays. An N:1‐15AA fragment binds to the 2,3‐diphosphoglycerate (2,3‐DPG) receptor locus of deoxy S with five to seven amino acids (AA) extending internally, while ten to eight AA remained external to deoxy S and inhibited polymerization by steric hindrance. A true mirror‐image peptide, corresponding to two N:1‐8AA + lysine (K) linked by coupler, binds to the 2,3‐DPG loci of two deoxy S molecules, tethering them together to form “binary complexes” incapable of entering the polymer chains. The reduction in the concentration of deoxy S available for extended chain formation decreased polymerization. We now report time:viscosity profiles of the sol‐gel transformation of purified solutions of deoxy S with and without peptides and studies of the gel solidity at equilibrium. Samples with peptides had longer lag times than controls of similar deoxy S concentrations. The mirror‐image peptide was a more effective inhibitor than the N:1‐15AA peptide. When the mirror‐image peptide was present in peptide:hemoglobin molar ratios of 0.25‐1:1, the increases in lag time were equivalent to decreasing the deoxy S concentrations by 15–25%, comparable to projected major therapeutic effects. Gel solidity, determined by yield temperature, was less in the sample with mirror‐image peptide compared to control. These results support the proposed mechanisms of inhibition of deoxy S polymerization by band 3 peptides. © 1993 Wiley‐Liss, Inc.