Stair Jacqueline L, White Brianna R, Rowland Adam, Holcombe James A
Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, USA.
J Comb Chem. 2006 Nov-Dec;8(6):929-34. doi: 10.1021/cc060100m.
An electrothermal vaporizer inductively coupled plasma mass spectrometer (ETV-ICPMS) was used to quantitatively screen metals bound to single polystyrene (TentaGel) beads with immobilized oligopeptides. Tests were performed using ETV-ICPMS to screen a series of identical beads as well as a series of combinatorial library beads exposed to a multimetal solution composed of Mg2+, Mn2+, Ni2+, Cu2+, Cd2+, Eu2+, and Pb2+. The residual metal content remaining bound to the beads after acid extractions was also analyzed by solid sampling of the entire bead using oxygen ashing in the ETV. Nine beads (80 mesh, 0.25 mmol g(-1) nominal capacity) containing covalently attached polyaspartic acid (PLAsp; n = 20) showed metal extract concentrations in the range of 4-130 ng mL(-1). After normalizing by bead volume, the precision of capacity measurements in a single bead (7-14%) was primarily dictated by analysis error and contributions from bead diameter measurement with negligible contributions, surprisingly, from variations in site density from bead to bead. A sample combinatorial library of the sequence GXXGXXGXXGXX (X = cysteine, aspartic acid, or glutamic acid and G = glycine) (60 mesh, 0.25 mmol g(-1) nominal capacity) was also used to demonstrate the utility of this method. Metal extract concentrations ranged from 1 to 1300 ng mL(-1) with significant concentration variation between beads, indicating the individual selectivity on each bead. For these larger beads, analysis precision (i.e., capacity precision) was further improved to 3-10% due to the overall increase in bead metal content. Through metal extract determinations, ETV-ICPMS was shown to be a viable nondestructive tool for full metal characterization of "hit" sequences belonging to a combinatorial library.
采用电热蒸发器电感耦合等离子体质谱仪（ETV-ICPMS）对与固定化寡肽结合的单聚苯乙烯（TentaGel）微珠上的金属进行定量筛选。使用ETV-ICPMS进行测试，以筛选一系列相同的微珠以及一系列暴露于由Mg2+、Mn2+、Ni2+、Cu2+、Cd2+、Eu2+和Pb2+组成的多金属溶液中的组合文库微珠。通过在ETV中使用氧灰化对整个微珠进行固体采样，还分析了酸提取后仍与微珠结合的残留金属含量。九个含有共价连接的聚天冬氨酸（PLAsp；n = 20）的微珠（80目，标称容量0.25 mmol g(-1)）显示金属提取物浓度在4 - 130 ng mL(-1)范围内。通过微珠体积归一化后，单个微珠容量测量的精度（7 - 14%）主要由分析误差和微珠直径测量的贡献决定，令人惊讶的是，微珠之间位点密度的变化贡献可忽略不计。还使用了序列为GXXGXXGXXGXX（X = 半胱氨酸、天冬氨酸或谷氨酸，G = 甘氨酸）（60目，标称容量0.25 mmol g(-1)）的样本组合文库来证明该方法的实用性。金属提取物浓度范围为1至1300 ng mL(-1)，微珠之间存在显著的浓度差异，表明每个微珠具有个体选择性。对于这些较大的微珠，由于微珠金属含量的总体增加，分析精度（即容量精度）进一步提高到3 - 10%。通过金属提取物测定，ETV-ICPMS被证明是一种可行的非破坏性工具，可用于对组合文库中“命中”序列进行全金属表征。
