Skip to main content
SpringerLink
Log in

High Throughput Analysis and Purification in Support of Automated Parallel Synthesis

  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

Rapid reverse-phase analytical and preparative HPLC methods havebeen developed for application to parallel synthesis libraries.Gradient methods, short columns, and high flow rates allowanalysis of over 300 compounds per day on a single system, orpurification of up to 200 compounds per day on a singlepreparative system. Hardware and software modifications allowcontinuous unattended use for maximum efficiency and throughput.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Balkenhohl, F., Bussche-Hunnefeld, C., Lansky, A. and Zechel, C., Combinatorial synthesis of small organicmolecules, Angew. Chem., Int. Ed. Engl., 35 (1996) 2289–2337.

    Article  Google Scholar 

  2. Fruchtel, F. and Jung, G., Organic chemistry on solid supports, Angew. Chem., Int. Ed. Engl., 35 (1996) 17–42.

    Article  Google Scholar 

  3. Thomson, L. and Ellman, J., Synthesis and applications of small molecule libraries, Chem. Rev., 96 (1996) 555–600.

    Article  Google Scholar 

  4. Gordon, E.M., Gallop, M.A. and Patel, D.V., Strategy and tactics in combinatorial organic synthesis: Applications to drug discovery, Acc. Chem. Res., 29 (1996) 144–154.

    Article  CAS  Google Scholar 

  5. Gallop, M.A., Barrett, R.W., Dower, W.J., Fodor, S.P.A. and Gordon, E.M., Applications of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries, J. Med. Chem., 37 (1994) 1233–1251.

    Article  CAS  PubMed  Google Scholar 

  6. Lam, K.S., Salmon, S.E., Hersh, E.M., Hruby, V.J., Kazmierski, W.M. and Knapp, R.J., A new type of synthetic peptide library for identifying ligand-binding activity, Nature, 354 (1991) 82–84.

    Article  CAS  PubMed  Google Scholar 

  7. Houghten, R.A., Pinilla, C., Blondelle, S.E., Appel, J.R., Dooley, C.T. and Cuervo, J.H., Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery, Nature, 345 (1991) 84–86.

    Article  Google Scholar 

  8. Zhao, P-L., Nachbar, R.B., Bolognese, J.A. and Chapman, K., Two new criteria for choosing sample size in combinatorial chemistry, J. Med. Chem., 39 (1996) 350–352.

    Article  CAS  PubMed  Google Scholar 

  9. Ni, Z.-J., Maclean, D., Holmes, C.P., Murphy, M.M., Ruhland, B., Jacobs, J. W., Gordon, E.M. and Gallop, M.A., Versatile approach to encoding combinatorial organic synthesis using chemically robust secondary amine tags, J. Med. Chem., 39 (1996) 1601–1608.

    Article  CAS  PubMed  Google Scholar 

  10. Kerr, J.M., Banville, S.C. and Zuckermann, R.N., Encoded combinatorial peptide libraries containing non-natural amino acids, J. Am. Chem. Soc., 115 (1993) 2529–2531.

    Article  CAS  Google Scholar 

  11. Baldwin, J.J., Burnbaum, J.J., Henderson, I. and Ohlmeyer, M.H., Synthesis of a small molecule combinatorial library encoded with molecular tags, J. Am. Chem. Soc., 117 (1995) 5588–5589.

    Article  CAS  Google Scholar 

  12. Ohlmeyer, M.H.J., Swanson, R.N., Dillard, L.W., Reader, J.C., Asouline, G., Kobayashi, R., Wigler, M. and Still, W.C., Complex synthetic chemical libraries indexed with molecular tags, Proc. Natl. Acad. Sci. USA, 90 (1993) 10922–10926.

    Article  CAS  PubMed  Google Scholar 

  13. Nicolaou, K.C., Xiao, X.-Y., Parandoosh, Z., Senyei, A. and Nova, M.P., Radiofrequency encoded combinatorial chemistry, Angew. Chem., Int. Ed. Engl., 34 (1995) 2289–2291.

    Article  CAS  Google Scholar 

  14. Czarnik, A.W., Encoding methods in combinatorial chemistry, Curr. Opin. Chem. Biol., 1 (1997) 60–66.

    Article  CAS  PubMed  Google Scholar 

  15. Cargill, J. and Maiefski, R., Automated combinatorial chemistry on solid phase, Lab. Robotics Autom., 8 (1996) 139–148.

    Article  CAS  Google Scholar 

  16. DeWitt, S.H. and Czarnik, A.W., Combinatorial organic synthesis using Parke-Davis's DIVERSOMER method, Acc. Chem. Res., 29 (1996) 114–122.

    Article  CAS  Google Scholar 

  17. Lawrence, R.M., Fryszman, O.M., Poss, M.A., Biller, S.A. and Weller, H.N., Automated preparation and purification of amides, Proc. Int. Symp. Lab. Autom. Robotics, (1995) 211–220.

  18. Lawrence, R.M., Biller, S. A., Fryszman, O.M. and Poss, M.A., Automated synthesis and purification of amides: Exploitation of automated solid phase extraction in organic synthesis, Synthesis, (1997) 553–558.

  19. Weller, H.N., Automated hands-on HPLC for nonspecialists, LC-GC, 10 (1992) 698–704.

    CAS  Google Scholar 

  20. Kirkland, J.J., HPLC method development: Practical aspects of increasing analysis speed while maintaining separation resolution, J. Chromatogr. Sci., 31 (1993) 493–497.

    CAS  Google Scholar 

  21. Dolan, J.W. and Snyder, L.R., Troubleshooting LC Systems, Humana Press, Totowa, NJ, 1989, pp. 486–488.

    Google Scholar 

  22. Zeng, L., Burton, L., Yung, K., Shushan, B. and Kassel, D. B., An automated analytical/preparative HPLC/MS system for the rapid characterization and purification of compound libraries, J. Chromatogr. A, in press.

Download references

Author information

Authors and Affiliations

  1. Combinatorial Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, NJ, 08543-4000, U.S.A

    Harold N. Weller & Marian G. Young

  2. Instrument Development Group, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, NJ, 08543-4000, U.S.A

    Stephen J. Michalczyk & Gary H. Reitnauer

  3. YMC Inc., 3233 Burnt Mill Drive, Wilmington, NC, 28403, U.S.A

    Robert S. Cooley & Peter C. Rahn

  4. Shimadzu Scientific Instruments Inc., 7102 Riverwood Drive, Columbia, MD, 21046-2502, U.S.A

    Dana J. Loyd, Dario Fiore & Steven J. Fischman

Authors
  1. Harold N. Weller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marian G. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephen J. Michalczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gary H. Reitnauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert S. Cooley
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peter C. Rahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dana J. Loyd
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dario Fiore
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Steven J. Fischman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Weller, H.N., Young, M.G., Michalczyk, S.J. et al. High Throughput Analysis and Purification in Support of Automated Parallel Synthesis. Mol Divers 3, 61–70 (1997). https://doi.org/10.1023/A:1009636725336

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1009636725336

Search

Navigation