The advantage of being virtual - Target-induced adaptation and selection in dynamic combinatorial libraries

Chemistry - A European Journal

Volumn 10, Issue 10, 2004, Pages 2565-2580

  Severin, Kay ^a  

^a EPFL   (Switzerland)

Author keywords

Combinatorial chemistry; Dynamic chemistry; Host guest chemistry; Networks; Numerical simulations

Indexed keywords

COMPUTER SIMULATION; TOPOLOGY;

DYNAMIC COMBINATORIAL LIBRARIES (DCL); NETWORK TOPOLOGY;

COMBINATORIAL MATHEMATICS;

ACCURACY; ADAPTATION; ARTICLE; BINDING AFFINITY; CONCENTRATION RESPONSE; DISSOCIATION CONSTANT; EXPERIMENTAL DESIGN; MATHEMATICAL COMPUTING; MOLECULAR DYNAMICS; MOLECULAR EVOLUTION; PARAMETER; SIMULATION; SYSTEM ANALYSIS; TECHNIQUE;

EID: 2942551201     PISSN: 09476539     EISSN: None     Source Type: Journal    
DOI: 10.1002/chem.200305660     Document Type: Article

References (91)

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69. The following publications contain experimental data, which are supplemented by theoretical analyses: a) Z. Grote, R. Scopelliti, K. Severin, Angew. Chem. 2003, 115, 3951-3955; Angew. Chem. Int. Ed. 2003, 42, 3821-3825; b) H. J. Cooper, M. A. Case, G. L. McLendon, A. G. Marshall, J. Am. Chem. Soc. 2003, 125, 5331-5339; c) J. D. Cheeseman, A. D. Corbett, R. Shu, J. Croteau, J. L. Gleason, R. J. Kazlauskas, J. Am. Chem. Soc. 2002, 124, 5692-5701; A. V. Eliseev, M. I. Nelen, Chem. Eur. J. 1998, 4, 825-834.
70. The following publications contain experimental data, which are supplemented by theoretical analyses: a) Z. Grote, R. Scopelliti, K. Severin, Angew. Chem. 2003, 115, 3951-3955; Angew. Chem. Int. Ed. 2003, 42, 3821-3825; b) H. J. Cooper, M. A. Case, G. L. McLendon, A. G. Marshall, J. Am. Chem. Soc. 2003, 125, 5331-5339; c) J. D. Cheeseman, A. D. Corbett, R. Shu, J. Croteau, J. L. Gleason, R. J. Kazlauskas, J. Am. Chem. Soc. 2002, 124, 5692-5701; A. V. Eliseev, M. I. Nelen, Chem. Eur. J. 1998, 4, 825-834.
71. The following publications contain experimental data, which are supplemented by theoretical analyses: a) Z. Grote, R. Scopelliti, K. Severin, Angew. Chem. 2003, 115, 3951-3955; Angew. Chem. Int. Ed. 2003, 42, 3821-3825; b) H. J. Cooper, M. A. Case, G. L. McLendon, A. G. Marshall, J. Am. Chem. Soc. 2003, 125, 5331-5339; c) J. D. Cheeseman, A. D. Corbett, R. Shu, J. Croteau, J. L. Gleason, R. J. Kazlauskas, J. Am. Chem. Soc. 2002, 124, 5692-5701; A. V. Eliseev, M. I. Nelen, Chem. Eur. J. 1998, 4, 825-834.
72. J. S. Moore, N. W. Zimmerman, Org. Lett. 2000, 2, 915-918.
73. For the present discussion it is assumed that every building block of a DCL of type B is able to associate with every other building block. Depending on the type of interaction that is used to link the subunits, this is not necessarily the case.
74. It should be noted that in principle, all these types of DCL can be comprised of linear and/or cyclic assemblies - the graphical focus on cyclic assemblies in Scheme 1 was chosen arbitrarily.
75. An alternative definition of the selectivity factor would be the ratio of amplification factors but the conclusions/trends are the same, regardless of the definition.
76. All simulations were performed with Gepasi, version 3.30. The steady-state concentrations were calculated using the DCL models described in the text and the Newton algorithm that is implemented in the program. a) P. Mendes, Comput. Appl. Biosci. 1993, 9, 563-571; b) P. Mendes, Trends Biochem. Sci. 1997, 22, 361-363.
77. All simulations were performed with Gepasi, version 3.30. The steady-state concentrations were calculated using the DCL models described in the text and the Newton algorithm that is implemented in the program. a) P. Mendes, Comput. Appl. Biosci. 1993, 9, 563-571; b) P. Mendes, Trends Biochem. Sci. 1997, 22, 361-363.
78. In Schemes 2,4, and 5 the targets are shown as a substrate with the DCL members acting as receptors. The results of the simulations are equally valid for the reverse situation.
79. t=[AA] + [AAT].
80. Simulations about the reversible assembly of A and B to form AA, BB and AB (without a target) were recently published by Isaacs: A. Wu, L. Isaacs, J. Am. Chem. Soc. 2003, 125, 4831-4835.
81. i=15 mM.
82. The term "virtual combinatorial library" (VCL) was introduced in 1997 by Lehn (see ref. [6c]).
83. As described for Model 4, the simulation focuses on the dimeric receptors and does not include the possibility that the target binds to the monomeric building blocks.
84. For a theoretical treatment of the concentration dependence of macrocyclizations see: G. Ercolani, L. Mandolini, P. Mencarelli, S. Roelens, J. Am. Chem. Soc. 1993, 115, 3901-3908.
85. The washing step can be performed under conditions that are quite different from the equilibration conditions. To ensure that the weak binders are partially removed, it would be possible to decrease the binding constants by variation of the solvent polarity or the pH.
86. A notable exception is described in reference [8]: the addition of sodium ions as a target was shown to increase the relative amount of a cyclic pentamer over a tetramer and a trimer.
87. The imines were generated by condensation of a diamine and a set of ketones or aldehydes. Prior to analysis, the imines were reduced in situ to the corresponding amines.
88. J. R. Nitschke, J.-M. Lehn, Proc. Natl. Acad. Sci. USA 2003, 100, 11 970-11 974.
89. M. A. Case, G. L. McLendon, J. Am. Chem. Soc. 2000, 122, 8089-8090.
90. It should be pointed out that there are several other variations of DCLs that were not discussed in this analysis. Apart from DCLs of type C (which should display the characteristics of both A and B), there is the possibility of using assembly reactions that are chemically orthogonal to each other (e.g. metal-ligand binding and imine bond formation; see: V. Goral, M. I. Nelen, A. V. Eliseev, J.-M. Lehn, Proc. Natl. Acad. Sci. USA 2001, 98, 1347-1352. Furthermore, one could couple a DCL with kinetically controlled reactions as discussed in reference [22c]. And these are just two recent developments in a rapidly evolving field.
91. The statement that the addition of a target will shift the equilibrium toward the DCL member that binds the target most efficiently can be found in the references [11], [17a], [19a], [22c], among others. For a recent overview about DCLs entitled "Amplification of the Fittest" see: M. Freemantle, Chem. Eng. News 2002, Sept. 2, 31-33.