An alkylsilyl-tethered, high-capacity solid support amenable to diversity-oriented synthesis for one-bead, one-stock solution chemical genetics

Journal of Combinatorial Chemistry

Volumn 3, Issue 3, 2001, Pages 312-318

  Tallarico, John A ^a   Depew, Kris M ^b   Pelish, Henry E ^b   Westwood, Nicholas J ^a   Lindsley, Craig W ^b   Shair, Matthew D ^b   Schreiber, Stuart L ^a,b   Foley, Michael A ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b HARVARD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKYNE; BROMINE; MICROSPHERE; PLANT RESIN; POLYSTYRENE DERIVATIVE; SILANE DERIVATIVE;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DELIVERY SYSTEM; DRUG DESIGN; INSTRUMENTATION; METHODOLOGY; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ALKYNES; BROMINE; DRUG DELIVERY SYSTEMS; DRUG DESIGN; MICROSPHERES; MOLECULAR STRUCTURE; POLYSTYRENES; RESINS, PLANT; SILANES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0035351150     PISSN: 15204766     EISSN: None     Source Type: Journal    
DOI: 10.1021/cc000107i     Document Type: Article

References (61)

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11. Currently we use a modification of the binary encoding method first described by Still to elucidate the chemical history of each synthesis bead. Ohlmeyer, M. H.; Swanson, R. N.; Dillard, L. W.; Reader, J. C.; Asouline, G.; Kobayashi, R.; Still, W. C. Proc. Natl. Acad. Sci. 1993, 90, 10922-10926. Modifications of this technique will be disclosed soon.
12. The 50 nmol of small molecule will give rise to a 5 mM stock solution in 10 μL of DMSO. Our current infrastructure readily supports the automated handling of these volumes of reagents and solvents for library arraying requirements and biological assays.
13. By use of robotic pin-transfer methods, our largest pin-transfer array consumes approximately 100 nL of stock DMSO solution upon each use. For the process of compound printing (see ref 5), approximately 1 nL of stock solution is removed from each well in a typical source plate.
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15. For an example of a high-capacity bead using heteroatom-grafted dendrimers, see the following. Fromont, C.; Bradley, M. J. Chem. Soc., Chem. Commun. 2000, 283-284. RAPP Polymere GmbH offers large (500-560 μm) aminomethyl functionalized at the 80-110 nmol/bead level; however, this resin would require "grafting" the appropriate linker for use in library synthesis (see footnote 14).
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53. The volume of a solvent used in each washing step is approximately 10 mL/g of resin.
54. This reagent is approximately a 7:3 mixture of HF and pyridine. This reagent can be further buffered with additional pyridine in the cleavage cocktail.
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