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Bio‐affinity characterization mass spectrometry
Author(s) -
Bruce James E.,
Anderson Gordon A.,
Chen Ruidan,
Cheng Xueheng,
Gale David C.,
Hofstadler Steven A.,
Schwartz Brenda L.,
Smith Richard D.
Publication year - 1995
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.1290090805
Subject(s) - chemistry , fourier transform ion cyclotron resonance , characterization (materials science) , mass spectrometry , electrospray ionization , non covalent interactions , electrospray , resolution (logic) , combinatorial chemistry , chromatography , analytical chemistry (journal) , nanotechnology , molecule , hydrogen bond , organic chemistry , computer science , materials science , artificial intelligence
A new approach, bio‐affinity characterization mass spectrometry (BACMS), aimed at providing a more rapid, sensitive and potentially more flexible alternative to techniques presently employed for the characterization of noncovalent interactions in mixtures, such as would be encountered in combinatorial chemistry, is presented. BACMS avoids some of the difficulties and potential artifacts associated with affinity chromatography since the noncovalent associations occur in solution; thus, BACMS avoids the requirement of solid support media and the development of non‐interfering linker species. This paper describes the conceptual basis for the methodology and its potential use in applications which include the screening of high affinity ligands in support of new drug development. BACMS exploits new Fourier‐transform ion cyclotron resonance (FTICR) mass spectrometry technologies which, when coupled to electrospray ionization (ESI), allow the investigation of specific noncovalent complexes formed in solution. BACMS utilizes the well‐known attributes of FTICR, such as the high resolution mass analysis and (MS) n ( n ⩾ 2) capabilities; however, it is even more directly a result of recently developed techniques involving quadrupolar excitation, such as selected‐ion accumulation. These tools are demonstrated and the results illustrate the extraordinary sensitivity achievable (solution concentrations of 1 × 10 −9 M without the use of separations prior to ESI). Thus, the new capabilities demonstrated here, in conjunction with ESI, will be useful for the investigation of very low relative concentration noncovalent association directly from solution, and promote a faster alternative for combinatorial mixture screening and analysis.