Research Focus

Antibody Catalysis, Organic Synthesis and prodrug therapy

Research activities in our laboratory include antibody catalysis, total synthesis of naturally occurring compounds and their analogs, methodology development and prodrug therapy. Antibody catalyzed reactions are performed to produce the chiral starting materials that are then converted to the natural products by chemical transformations. On the prodrug therapy topic, our main focus is on the synthesis of prodrugs, construction of catalytic antibodies and enzymes that possess both the targeting and catalytic properties, and evaluation of prodrugs and catalysts.

Selected References

Goswami RK, Liu Y, Liu C, Lerner RA, Sinha SC. Synthesis and evaluation of the aldolase antibody-derived chemical-antibodies targeting alpha(5)beta(1) integrin. Mol Pharm. 2013, 10(2):538-43.

Axup JY, Bajjuri KM, Ritland M, Hutchins BM, Kim CH, Kazane SA, Halder R, Forsyth JS, Santidrian AF, Stafin K, Lu Y, Tran H, Seller AJ, Biroc SL, Szydlik A, Pinkstaff JK, Tian F, Sinha SC, Felding-Habermann B, Smider VV, Schultz PG. Synthesis of site-specific antibody-drug conjugates using unnatural amino acids. Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16101-6.

Liu Y, Bajjuri KM, Liu C, Sinha SC. Targeting cell surface alpha(v)beta(3) integrin increases therapeutic efficacies of a legumain protease-activated auristatin prodrug. Mol Pharm. 2012 Jan 1;9(1):168-75.

Liu Y, Jiang P, Capkova K, Xue D, Ye L, Sinha SC, Mackman N, Janda KD, Liu C. Tissue factor-activated coagulation cascade in the tumor microenvironment is critical for tumor progression and an effective target for therapy. Cancer Res. 2011 Oct 15;71(20):6492-502.

Goswami RK, Bajjuri KM, Forsyth JS, Das S, Hassenpflug W, Huang ZZ, Lerner RA, Felding-Habermann B, Sinha SC. Chemically programmed antibodies targeting multiple alpha(v) integrins and their effects on tumor-related functions in vitro. Bioconjug Chem. 2011 Aug 17;22(8):1535-44.

Bajjuri KM, Liu Y, Liu C, Sinha SC. The legumain protease-activated auristatin prodrugs suppress tumor growth and metastasis without toxicity. ChemMedChem. 2011 Jan 3;6(1):54-9.

Nakamaru-Ogiso E, Kao MC, Chen H, Sinha SC, Yagi T, Ohnishi T. The membrane subunit NuoL(ND5) is involved in the indirect proton pumping mechanism of Escherichia coli complex I. J Biol Chem. 2010 Dec 10;285(50):39070-8.

Links

The Skaggs Institute Scientific Report