Enjalbal Christine, Maux Delphine, Combarieu Robert, Martinez Jean, Aubagnac Jean-Louis
CNRS-UMR 5810, Laboratoire des Aminoacides, Peptides et Protéines, Universités Montpellier I et II, Place E. Bataillon, 34095 Montpellier Cedex 05, France.
J Comb Chem. 2003 Mar-Apr;5(2):102-9. doi: 10.1021/cc0200484.
Supported peptide and drug-like organic molecule libraries were profiled in single nondestructive imaging static secondary ion mass spectrometric experiments. The selective rupture of the bond linking the compound and the insoluble polymeric support (resin) produced ions that were characteristic of the anchored molecules, thus allowing unambiguous resin bead assignment. Very high sensitivity and specificity were obtained with such a direct analytical method, which avoids the chemical release of the molecules from the support. Libraries issued from either mix-and-split or parallel solid-phase organic syntheses were profiled, demonstrating the usefulness of such a technique for characterization and optimization during combinatorial library development. Moreover, the fact that the control was effected at the bead level whatever the structure and quantity of the anchored molecules allows the sole identification of active beads selected from on-bead screening. Under such circumstances, the time-consuming whole-library characterization could thus be suppressed, enhancing the throughput of the analytical process.
在单次无损成像静态二次离子质谱实验中，对负载型肽和类药物有机分子文库进行了分析。连接化合物与不溶性聚合物载体（树脂）的键的选择性断裂产生了锚定分子特有的离子，从而实现了对树脂珠的明确识别。这种直接分析方法具有非常高的灵敏度和特异性，避免了分子从载体上的化学释放。对通过混合拆分或平行固相有机合成得到的文库进行了分析，证明了该技术在组合文库开发过程中用于表征和优化的实用性。此外，无论锚定分子的结构和数量如何，均在珠子水平上进行对照，这使得能够唯一识别从珠上筛选中选出的活性珠子。在这种情况下，可以省去耗时的全文库表征，提高分析过程的通量。
