Determining synthetic failures in combinatorial libraries by hybrid gas-phase separation methods
A combinatorial tripeptide library having the general form D-Glu-Xxx-Xxx-CONH 2 has been synthesized using a standard mix and split synthetic protocol that is expected to produce 676 components. All components of the mixture were analyzed using a new high-resolution ion mobility/time-of-flight mass...
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| Veröffentlicht in: | Journal of the American Society for Mass Spectrometry 2000-04, Vol.11 (4), p.352-355 |
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| container_title | Journal of the American Society for Mass Spectrometry |
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| creator | Srebalus, Catherine A Li, Jianwei Marshall, William S Clemmer, David E |
| description | A combinatorial tripeptide library having the general form
D-Glu-Xxx-Xxx-CONH
2 has been synthesized using a standard mix and split synthetic protocol that is expected to produce 676 components. All components of the mixture were analyzed using a new high-resolution ion mobility/time-of-flight mass spectrometer coupled with an electrospray ionization source. In this approach ions are separated by differences in their gas-phase mobilities prior to being introduced into the mass spectrometer for mass-to-charge analysis. The peptide library includes a wide range of different sequence, structural, and stereo isomers; trends in the number of expected and resolved isomers that are observed at each
m/z ratio allow specific synthetic steps that have failed to be identified, even in the presence of other isomers. Information about the relative abundances of different isomers should dramatically improve the reliability of binding affinity studies from direct analysis of mixtures. |
| doi_str_mv | 10.1016/S1044-0305(00)00099-4 |
| format | Article |
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| source | MEDLINE; SpringerNature Journals; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Biological and medical sciences Chemistry Chromatography, Gas Exact sciences and technology General pharmacology Isomerism Mass Spectrometry Medical sciences Organic chemistry Peptide Library Peptides Peptides - chemical synthesis Pharmacology. Drug treatments Physicochemical properties. Structure-activity relationships Preparations and properties |
| title | Determining synthetic failures in combinatorial libraries by hybrid gas-phase separation methods |
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