Imaging combinatorial libraries by mass spectrometry: from peptide to organic-supported syntheses.
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.
Enjalbal
Christine
C
CNRS-UMR 5810, Laboratoire des Aminoacides, Peptides et Protéines, Universités Montpellier I et II, Place E. Bataillon, 34095 Montpellier Cedex 05, France.
Maux
Delphine
D
Combarieu
Robert
R
Martinez
Jean
J
Aubagnac
Jean-Louis
JL
D000577:Amides / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D007091:Image Processing, Computer-Assisted; D013058:Mass Spectrometry; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis; D011137:Polystyrenes; D012117:Resins, Synthetic
D000577:Amides; D019151:Peptide Library; D010455:Peptides; D011137:Polystyrenes; D012117:Resins, Synthetic