CONTACT INFORMATION

Isaac Krauss
Edison-Lecks 226
781-736-2574
kraussi@brandeis.edu

Group Web site

Isaac Krauss

krauss.jpg

Isaac Krauss

Assistant Professor of Chemistry
Ph.D., Columbia University

Our lab studies interesting problems in organic synthesis and chemical biology.
Our chemical biology program is directed at the design and synthesis of carbohydrate clusters which mimic important binding surfaces in biology. One target is the portion of HIV protein gp120 which is bound by 2G12, a broadly-neutralizing antibody which protects against the virus. Good mimics of this glycocluster have potential as HIV vaccines. Rather than design and test individual glycoclusters, we are using a directed evolution-based approach, in which the best gp120 mimics are selected from a diverse glycocluster library by their ability to bind 2G12. This directed evolution is accomplished by attachment of sugars to a library of DNA sequences using click chemistry, a technique which we term SELMA (SELection with Modified Aptamers). We are also applying SELMA and related methods to other problems in molecular recognition.
glycoDNAs

The SELMA Method

 BromophycolideAOur organic synthesis program is focused on study of mechanistically-interesting reactions which enable access to structural motifs that are difficult to access by other methods. One example is homoallylation reactions. Although a great number of allylation methods are known, known methods for synthesis of the one-carbon homologs are very limited, despite their utility as precursors of stereodefined tetrahydrofurans and tetrahydropyrans. In addition to development of these methods, we are also interested in their application to synthesis of interesting target structures.

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 Sample of Recent Publications

  1. Boron Carboxylate Catalysis of Homoallylboration
    Dugas, G. J.; Lam, Y.-H.; Houk, K. N.; Krauss, I. J. J. Org. Chem. 2014 , ASAP (Featured Article)

  2. "Directed Evolution of Multivalent Glycopeptides Tightly Recognized by HIV Antibody 2G12"
    Horiya, S.; Bailey, J.; Temme, J.; Guillen Schlippe, Y.; Krauss, I. J. Am. Chem. Soc., Just accepted (Highlighted in C&E News, 3/31/14)
  3. High Temperature SELMA: Evolution of DNA-Supported Oligomannose Clusters Which Are Tightly Recognized by HIV bnAb 2G12Temme, S. J.; MacPherson, I. S.; DeCourcey, J. F.; Krauss, I. J. J. Am. Chem. Soc. 2014 , 136(5), 1726-1729.
  4. Directed Evolution of 2G12-Targeted Nonamannose Glycoclusters by SELMA

    Temme, J. S.; Drzyzga, M.; MacPherson, I. S.; Krauss, I. J. Chem. - Eur. J. 2013 , 19(51), 17291-17295.
  5. Enantioselective Homocrotylboration of Aliphatic Aldehydes

    Lin, H.; Pei, W.; Wang, H.; Houk, K. N.; Krauss, I. J. J. Am. Chem. Soc. 2013, 135(1), 82-85. (Highlighted in Synfacts 2013, 9, 315).
  6. Homoallylboration and Homocrotylboration of Aldehydes

    Pei, W.; Krauss, I. J J. Am. Chem. Soc. 2011, 133(46), 18514-18517. (Highlighted in Synfacts 2012, 8, 203).
  7. Multivalent Glycocluster Design Through Directed Evolution

    MacPherson, I. S.; Temme. J. S.; Habeshian, S.; Felczak, K.; Pankiewicz, K.; Hedstrom, L.; Krauss, I. J Angew. Chem. Int. Ed. 2011, 50(47), 11238-11242.
  8. A Short Asymmetric Route to the Bromophycolide A and D Skeleton

    Lin, H.; Pochapsky, S.S.; Krauss, I. J Org. Lett. 2011, 13(5), 1222-1225.
  9. Enzyme-Instructed Molecular Self-assembly Confers Nanofibers and a Supramolecular Hydrogel of Taxol Derivative

    Gao, Y.; Kuang, Y.; Guo, Z-F.; Guo, Z.; Krauss, I. J.; Xu, Bing J. Am. Chem. Soc. 2009, 131(38), 13576-13577.
  10. Confirmation of the structures of synthetic derivatives of migrastatin in the light of recently disclosed crystallographically based claims

    Nagorny, P.; Krauss, I. J. Njardarson, J. T.; Perez, L.; Gaul, C.; Yang, G.; Ouerfelli, O.; Danishefsky, S. J. Tetrahedron Lett. 2010, 51(30), 3873-3875.
  11. Diverted Total Synthesis Leads to the Generation of Promising Cell-Migration Inhibitors for Treatment of Tumor Metastasis: In vivo and Mechanistic Studies on the Migrastatin Core Ether Analog

    Oskarsson, T.; Nagorny, P.; Krauss, I. J.; Perez, L.; Mandal, M.; Yang, G.; Ouerfelli, O.; Xiao, D.; Moore, M. S.; Massague, J.; Danishefskhy, S. J. J. Am. Chem. Soc. 2010, 132(9), 3224-3228.
  12. A New Model for the Presentation of Tumor-Associated Antigens and the Quest for an Anticancer Vaccine: A Solution to the Synthesis Challenge via Ring-Closing Metathesis

    Jeon, I.; Lee, D.; Krauss, I. J.; Danishefsky, S. J. J. Am. Chem. Soc. 2009, 131(40), 14337-14344.
  13. An oligosaccharide-based HIV-1 2G12 mimotope vaccine induces carbohydrate-specific antibodies that fail to neutralize HIV-1 virions

    Joyce, J. G.; Krauss, I. J.; Song, H. C.; Opalka, D. W.; Grimm, K. M.; Nahas, D. D.; Esser, M. T.; Hrin, R.; Feng, M.; Dudkin, V. Y.; Chastain, M.; Shiver, J. W.; Danishefsky, S. J. Proc. Natl. Acad. Sci. USA 2008, 105(41), 15684-15689.
  14. Total Synthesis of Spirotenuipesines A and B

    Dai, M.; Krauss, I. J.; Danishefsky, S. J. J. Org. Chem. 2008, 73(24), 9576-9583.
  15. Fully Synthetic Carbohydrate HIV Antigens Designed on the Logic of the 2G12 Antibody

    Krauss, I. J.; Joyce, J. G.; Finnefrock, A. C.; Song, H. C.; Dudkin, V. Y.; Geng, X.; Warren, J. D.; Chastain, M.; Shiver, J. W.; Danishefsky, S. J. J. Am. Chem. Soc. 2007, 129(36), 11042-11044.
  16. Total synthesis of (+)-isomigrastatin

    Krauss, I. J.; Mandal, M.; Danishefsky, S. J. Angew. Chem. Int. Ed. 2007, 46(29), 5576-5579.
  17. Highly Practical and Enantioselective Cu-Catalyzed Conjugate Addition of Alkylzinc Reagents to Cyclic Enones at Ambient Temperature

    Krauss, I. J.; Leighton, J. L. Org. Lett. 2003, 5(18), 3201-3203.
  18. Highly Regioselective and Diastereoselective Directed Hydroformylation of Allylic Ethers: A New Approach to Propionate Aldol Synthesis

    Krauss, I. J; Wang, C. C-Y.; Leighton, J. L. J. Am. Chem. Soc. 2000, 123(46), 11514-11515.