Abstract
The integration of mass spectrometry and combinatorial chemistry is becoming commonplace in many laboratory settings. Combinatorial chemistry provides a means for synthesis of mixtures of large numbers of compounds, thereby greatly increasing the diversity of molecular architectures available for screening. Mass spectrometry is being utilized as a rapid and sensitive tool not only to characterize combinatorial libraries, but also to aid in the identification of active compounds.
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References
1.
Gallop
M.A.
Barrett
R.W.
Dower
W.J.
Fodor
S.P.A.
Gordon
E.M.
, J. Med. Chem. 37 , 1233 (1994 ).
2.
Baum
R.M.
, Chem. Eng. News 72 , 20 (1994 ).
3.
Balkenhohl
F.
von dem Bussche-Hunnefeld
C.
Lansky
A.
Zechel
C.
, Angew. Chem. Int. Ed. Engl. 35 , 2289 (1996 ).
4.
Borman
S.
, Chem. Eng. News 74 , 29 (1996 ).
5.
Carell
T.
Wintner
E.A.
Sutherland
A.J.
Rebek
J.
Dunayevskiy
Y.M.
Vouros
P.
, Chem. Biol. 2 , 171 (1995 ).
6.
Hegy
G.
Gorlach
E.
Richmond
R.
Bitsch
F.
, Rapid Commun. Mass Spectrom. 10 , 1894 (1996 ).
7.
Meng
C.K.
Mann
M.
Fenn
J.B.
, Z. Phys. D—Atoms, Molecules and Clusters 10 , 361 (1988 ).
8.
Fenn
J.B.
Mann
M.
Meng
C.K.
Wong
S.F.
Whitehouse
C.M.
, Science 246 , 64 (1989 ).
9.
Karas
M.
Hillenkamp
F.
, Anal. Chem. 60 , 2299 (1988 ).
10.
Karas
M.
Bahr
U.
Ingendoh
A.
Hillenkamp
F.
, Angew. Chem. Int. Ed. Engl. 28 , 760 (1989 ).
11.
Zuckermann
R.N.
Kerr
J.M.
Siani
M.A.
Banville
S.C.
Santi
D.V.
, Proc. Natl. Acad. Sci. USA 89 , 4505 (1992 ).
12.
Boutin
J.A.
Hennig
P.
Lambert
P.-H.
Bertin
S.
Petit
L.
Mahieu
J.-P.
Serkiz
B.
Volland
J.-P.
Fauchere
J.-L.
, Anal. Biochem. 234 , 126 (1996 ).
13.
Andrews
P.C.
Boyd
J.
Loo
R. Ogorzalek
Zhao
R.
Zhu
C.-Q.
Grant
K.
Williams
S.
, in Techniques in Protein Chemistry V , Ed by
Crabb
J.W.
, Academic Press , San Diego, CA , p. 485 (1994 ).
14.
Andrews
P.C.
Leonard
D.M.
Cody
W.L.
Sawyer
T.K.
, in Methods in Molecular Biology: Peptide Analysis Protocols , Ed by
Dunn
B.M.
Pennington
M.W.
, Humana Press , Totowa, NJ , Vol. 36 , p. 305 (1994 ).
15.
Metzger
J.W.
Wiesmüller
K.H.
Stevanović
S.
Jung
G.
, in Peptides 1992 , Ed by
Schneider
C.H.
Eberle
A.N.
, ESCOM , Leiden, The Netherlands , p. 481 (1993 ).
16.
Stevanović
S.
Wiesmüller
K.H.
Metzger
J.
Becksickinger
A.G.
Jung
G.
, Bioorg. Med. Chem. Lett. 3 , 431 (1993 ).
17.
Metzger
J.W.
Wiesmüller
K.H.
Gnau
V.
Brunjes
J.
Jung
G.
, Angew. Chem. Int. Ed. Engl. 32 , 894 (1993 ).
18.
Metzger
J.W.
Stevanović
S.
Brunjes
J.
Wiesmüller
K.H.
Jung
G.
, Methods (San Diego) 6 , 425 (1994 ).
19.
Loo
J.A.
DeJohn
D.E.
Loo
R.R. Ogorzalek
Andrews
P.C.
, in Annual Reports in Medicinal Chemistry , Ed by
Bristol
J.A.
, Academic Press , San Diego, CA , Vol. 31 , p. 319 (1996 ).
20.
Boutin
J.A.
Fauchere
J.-L.
, Am. Biotech. Lab. 14 , 36 (1996 ).
21.
Mason
T.J.
Bennell
P.S.
Smart
S.S.
Valerio
R.M.
Bray
A.M.
Maeji
N.J.
Geysen
H.M.
, in Peptides 1994 (Proceedings of the Twenty-Third European Peptide Symposium) , Ed by
Maia
H.L.S.
, ESCOM , Leiden, The Netherlands , p. 94 (1995 ).
22.
Metzger
J.W.
Kempter
C.
Wiesmüller
K.H.
Jung
G.
, Anal. Biochem. 219 , 261 (1994 ).
23.
Dunayevskiy
Y.
Vouros
P.
Carell
T.
Wintner
E.A.
Rebek
J.
, Anal. Chem. 67 , 2906 (1995 ).
24.
Andrews
P.C.
, personal communication.
25.
Rourick
R.A.
Whitney
J.L.
Klohr
S.E.
Volk
K.J.
Kerns
E.H.
Lee
M.S.
, Proceedings of the 44th ASMS Conference on Mass Spectrometry and Allied Topics , Portland, OR , p. 1039 (1996 ).
26.
Dunayevskiy
Y.M.
Vouros
P.
Wintner
E.A.
Shipps
G.W.
Carell
T.
Rebek
J.
Jr
, Proc. Natl. Acad. Sci. USA 93 , 6152 (1996 ).
27.
Fang
A.S.
Vouros
P.
Stacey
C.C.
Kruppa
G.H.
Laukien
F.H.
Carell
T.
Winter
E.A.
Rebek
J.
Jr
, Proceedings of the 44th ASMS Conference on Mass Spectrometry and Allied Topics , Portland, OR , p. 1047 (1996 ).
28.
Winger
B.E.
Campana
J.E.
, Rapid Commun. Mass Spectrom. 10 , 1811 (1996 ).
29.
Metzger
J.
Kienle
S.
Wiesmüller
K.H.
, GIT-Fachz. Lab. 40 , 85 (1996 ).
30.
Nawrocki
J.P.
Wigger
M.
Watson
C.H.
Hayes
T.W.
Senko
M.W.
Benner
S.A.
Eyler
J.R.
, Rapid Commun. Mass Spectrom. 10 , 1860 (1996 ).
31.
Aubagnac
J.-L.
Calmes
M.
Daunis
J.
El Amrani
B.
Jacquier
R.
, in Peptides: Structure and Function (Proceedings of the Ninth American Peptide Symposium) , Ed by
Deber
C.M.
Hruby
V.J.
Kopple
K.D.
, Pierce Chemical Co. , Rockford, IL , p. 277 (1985 ).
32.
van Veelen
P.A.
Tjaden
U.R.
van der Greef
J.
, Rapid Commun. Mass Spectrom. 5 , 565 (1991 ).
33.
Egner
B.J.
Langley
G.J.
Bradley
M.
, J. Org. Chem. 60 , 2652 (1995 ).
34.
Zambias
R.A.
Boulton
D.A.
Griffin
P.R.
Tet. Lett. 35 , 4283 (1994 ).
35.
Haskins
N.J.
Hunter
D.J.
Organ
A.J.
Rahman
S.S.
Thom
C.
, Rapid Commun. Mass Spectrom. 9 , 1437 (1995 ).
36.
Brummel
C.L.
Vickerman
J.C.
Carr
S.A.
Hemling
M.E.
Roberts
G.D.
Johnson
W.
Weinstock
J.
Gaitanopoulos
D.
Benkovic
S.J.
Winograd
N.
, Anal. Chem. 68 , 237 (1996 ).
37.
Egner
B.J.
Cardno
M.
Bradley
M.
, J. Chem. Soc. Chem. Commun. , 2163 (1995 ).
38.
Lebl
M.
Krchnak
V.
Sepetov
N.F.
Nikolaev
V.
Stankova
M.
Kocis
P.
Patek
M.
Flegelova
Z.
Ferguson
R.
Lam
K.S.
, in Methods in Protein Structure Analysis , Ed by
Atassi
M.Z.
Appella
E.
, Plenum Press , New York , p. 335 (1995 ).
39.
Geysen
H.M.
Wagner
C.D.
Bodnar
W.M.
Markworth
C.J.
Parke
G.J.
Schoenen
F.J.
Wagner
D.S.
Kinder
D.S.
, Chem. Biol. 3 , 679 (1996 ).
40.
Brown
B.B.
Wagner
D.S.
Geysen
H.M.
, Molecular Diversity 1 , 4 (1995 ).
41.
Fitzgerald
M.C.
Harris
K.
Shevlin
C.G.
Siuzdak
G.
, Bioorg. Med. Chem. Lett. 6 , 979 (1996 ).
42.
Brummel
C.L.
Lee
I.N.W.
Zhou
Y.
Benkovic
S.J.
Winograd
N.
, Science 264 , 399 (1994 ).
43.
Benkovic
S.J.
Winograd
N.
Brummel
C.L.
Lee
I.N.W.
, “Method for identifying members of combinatorial libraries,” Patent Appl., PCT Int. Appl. W09525737 (1995 ).
44.
Drouot
C.
Enjalbal
C.
Fulcrand
P.
Martinez
J.
Aubagnac
J.-L.
Combarieu
R.
de Puydt
Y.
, Rapid Commun. Mass Spectrom. 10 , 1509 (1996 ).
45.
Youngquist
R.S.
Fuentes
G.R.
Lacey
M.P.
Keough
T.
, Rapid Commun. Mass Spectrom. 8 , 77 (1994 ).
46.
Youngquist
R.S.
Fuentes
G.R.
Lacey
M.P.
Keough
T.
, J. Am. Chem. Soc. 117 , 3900 (1995 ).
47.
Youngquist
R.S.
Fuentes
G.R.
Miller
C.M.
Ridder
G.M.
Lacey
M.P.
Keough
T.
, Proceedings of the 43rd ASMS Conference on Mass Spectrometry and Allied Topics , Atlanta, GA , p. 484 (1995 ).
48.
Dollinger
G.D.
Huebner
V.D.
, “Affinity selection of ligands by mass spectroscopy,” Patent Appl., PCT Int. Appl. WO 9622530 (1996 ).
49.
Huebner
V.
Dollinger
G.
Kaur
S.
McGuire
L.
Tang
D.
Siani
M.
Drummond
R.
Rosenburg
S.
, Presented at the Ninth Symposium of the Protein Society , Boston, MA (1995 ).
50.
Huebner
V.
Kaur
S.
McGuire
L.
Tang
D.
Dollinger
G.
, Proceedings of the 44th ASMS Conference on Mass Spectrometry and Allied Topics , Portland, OR , p. 748 (1996 ).
51.
Kaur
S.
Huebner
V.
Tang
D.
McGuire
L.
Drummond
R.
Csetjey
J.
Stratton-Thomas
J.
Rosenberg
S.
Figliozzi
G.
Banville
S.
Zuckermann
R.
Dollinger
G.
, Proceedings of the 43rd ASMS Conference on Mass Spectrometry and Allied Topics , Atlanta, GA , p. 30 (1995 ).
52.
Williams
K.P.
Evans
D.M.
Rosenberg
S.
Jindal
S.
, in Techniques in Protein Chemistry VII , Ed by
Marshak
D.R.
, Academic Press , San Diego, CA , p. 57 (1996 ).
53.
van Breemen
R.B.
Huang
C.-R.
Nikolic
D.
Woodbury
C.
Zhao
Y.-Z.
Venton
D.
, Proceedings of the 44th ASMS Conference on Mass Spectrometry and Allied Topics , Portland, OR , p. 749 (1996 ).
54.
van Breemen
R.B.
Huang
C.-R.
Nikolic
D.
Woodbury
C.
Zhao
Y.-Z.
Venton
D.
, Proceedings of the 44th ASMS Conference on Mass Spectrometry and Allied Topics , Portland, OR , p. 1031 (1996 ).
55.
Hales
N.J.
Clayton
E.
, “Affinity chromatographic method for screening combinatorial libraries,” Patent Appl., PCT Int. Appl. WO 9632642 (1995 ).
56.
Kelly
M.A.
Liang
H.B.
Sytwu
I.-I.
Vlattas
I.
Lyons
N.L.
Bowen
B.R.
Wennogle
L.P.
, Biochemistry 35 , 11747 (1996 ).
57.
Kassel
D.B.
Consler
T.G.
Shalaby
M.
Sekhri
P.
Gordon
N.
Nadler
T.
, in Techniques in Protein Chemistry VI , Ed by
Crabb
J.W.
, Academic Press , San Diego, CA , p. 39 (1995 ).
58.
Nedved
M.L.
Habibi-Goudarzi
S.
Ganem
B.
Henion
J.D.
, Anal. Chem. 68 , 4228 (1996 ).
59.
Smith
R.D.
Olivares
J.A.
Nguyen
N.T.
Udseth
H.R.
, Anal. Chem. 60 , 436 (1988 ).
60.
Smith
R.D.
Wahl
J.H.
Goodlett
D.R.
Hofstadler
S.A.
, Anal. Chem. 65 , A574 (1993 ).
61.
Lee
E.D.
Muck
W.
Henion
J.D.
Covey
T.R.
, J. Chromatogr. 458 , 313 (1988 ).
62.
Thibault
P.
Paris
C.
Pleasance
S.
, Rapid Commun. Mass Spectrom. 5 , 484 (1991 ).
63.
Valaskovic
G.A.
Kelleher
N.L.
McLafferty
F.W.
, Science 273 , 1199 (1996 ).
64.
Chu
Y.-H.
Whitesides
G.M.
, J. Org. Chem. 57 , 3524 (1992 ).
65.
Chu
Y.-H.
Avila
L.Z.
Biebuyck
H.A.
Whitesides
G.M.
, J. Med. Chem. 35 , 2915 (1992 ).
66.
Gomez
F.A.
Avila
L.Z.
Chu
Y.-H.
Whitesides
G.M.
, Anal. Chem. 66 , 1785 (1994 ).
67.
Chu
Y.-H.
Lees
W.J.
Stassinopoulos
A.
Walsh
C.T.
, Biochemistry 33 , 10616 (1994 ).
68.
Chu
Y.H.
Kirby
D.P.
Karger
B.L.
, J. Am. Chem. Soc. 117 , 5419 (1995 ).
69.
Chu
Y.H.
Dunayevskiy
Y.M.
Kirby
D.P.
Vouros
P.
Karger
B.L.
, J. Am. Chem. Soc. 118 , 7827 (1996 ).
70.
Smith
R.D.
Light-Wahl
K.J.
, Biol. Mass Spectrom. 22 , 493 (1993 ).
71.
Loo
J.A.
, Bioconj. Chem. 6 , 644 (1995 ).
72.
Bruce
J.E.
Anderson
G.A.
Chen
R.
Cheng
X.
Gale
D.C.
Hofstadler
S.A.
Schwartz
B.L.
Smith
R.D.
, Rapid Commun. Mass Spectrom. 9 , 644 (1995 ).
73.
Loo
J.A.
Hu
P.
Thanabal
V.
, Proceedings of the 43rd ASMS Conference on Mass Spectrometry and Allied Topics , Atlanta, GA , p. 35 (1995 ).
74.
Loo
J.A.
Hu
P.
McConnell
P.
Mueller
W.T.
Sawyer
T.K.
Thanabal
V.
, J. Am. Soc. Mass Spectrom. 8 , 234 (1997 ).
75.
Cheng
X.H.
Chen
R.D.
Bruce
J.E.
Schwartz
B.L.
Anderson
G.A.
Hofstadler
S.A.
Gale
D.C.
Smith
R.D.
Gao
J.M.
Sigal
G.B.
Mammen
M.
Whitesides
G.M.
, J. Am. Chem. Soc. 117 , 8859 (1995 ).
76.
Gao
J.
Cheng
X.
Chen
R.
Sigal
G.B.
Bruce
J.E.
Schwartz
B.L.
Hofstadler
S.A.
Anderson
G.A.
Smith
R.D.
Whitesides
G.M.
, J. Med. Chem. 39 , 1949 (1996 ).
77.
Kassel
D.B.
Green
M.D.
Wehbie
R.S.
Swanstrom
R.
Berman
J.
, Anal. Biochem. 228 , 259 (1995 ).
78.
Kupke
T.
Kempter
C.
Jung
G.
Gotz
F.
, J. Biol. Chem. 270 , 11282 (1995 ).
79.
Till
J.H.
Annan
R.S.
Carr
S.A.
Miller
W.T.
, J. Biol. Chem. 269 , 7423 (1994 ).
80.
Holt
R.M.
Newman
M.J.
Pullen
F.S.
Richards
D.S.
Swanson
A.G.
, J. Mass Spectrom. 32 , 64 (1997 ).