This program has three broad goals. The first is the development of new chemistry, (both in terms of strategy as well as specific reactions) to assist in the synthesis of complex target systems. The second is the application of this chemistry to the synthesis of potentially useful anticancer agents. Finally we hope to evaluate, albeit on a qualitative basis some notions as to the mode of action of these substances. Natural products and structure related to natural products provide the focus for our synthetic efforts. Included in the collection of goals on which we will concentrate are: (i) mitomycin K, (ii) FR-900482; (iii) calicheamicin; (iv) dynemycin; (v) bent anthracyclines (for a relatively simple member see SF 2315); (vi) aryl C glycosides (such as gilvocarcin); (vii) adriamycin analogs with sharply modified carbohydrate sectors; (viii) myrocin C; (ix) mamanuthaquinone; (x) pancrastatin; (xi) varacin; and (xii) gelsemine . All except xii have known cytotoxic properties. In addition to pursuing total synthesis and analog synthesis, these studies will be toward gaining an insight into the chemistry of the drug candidate structure. It is anticipated that such studies will help to clarify chemical possibilities which might be of relevance to drug activation. Another area will be that of carbohydrate DNA interactions. Since so many an DNA targeted drugs possess a saccharide as well as an aglycone component, this is a most important question for the design of future drugs of greater selectivity.
| Rao, Thapi Dharma; Fernández-Tejada, Alberto; Axelrod, Abram et al. (2017) Antibodies Against Specific MUC16 Glycosylation Sites Inhibit Ovarian Cancer Growth. ACS Chem Biol 12:2085-2096 |
| O'Cearbhaill, Roisin E; Ragupathi, Govind; Zhu, Jianglong et al. (2016) A Phase I Study of Unimolecular Pentavalent (Globo-H-GM2-sTn-TF-Tn) Immunization of Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer in First Remission. Cancers (Basel) 8: |
| Danishefsky, Samuel J; Shue, Youe-Kong; Chang, Michael N et al. (2015) Development of Globo-H cancer vaccine. Acc Chem Res 48:643-52 |
| (2015) Voices of chemical biology. Nat Chem Biol 11:378-9 |
| Fernández-Tejada, Alberto; Brailsford, John; Zhang, Qiang et al. (2015) Total synthesis of glycosylated proteins. Top Curr Chem 362:1-26 |
| Wilson, Rebecca M; Danishefsky, Samuel J (2013) A vision for vaccines built from fully synthetic tumor-associated antigens: from the laboratory to the clinic. J Am Chem Soc 135:14462-72 |
| Wang, Ping; Dong, Suwei; Brailsford, John A et al. (2012) At last: erythropoietin as a single glycoform. Angew Chem Int Ed Engl 51:11576-84 |
| Brailsford, John A; Danishefsky, Samuel J (2012) Probing the stability of nonglycosylated wild-type erythropoietin protein via reiterative alanine ligations. Proc Natl Acad Sci U S A 109:7196-201 |
| Wu, Xiangyang; Stockdill, Jennifer L; Park, Peter K et al. (2012) Expanding the limits of isonitrile-mediated amidations: on the remarkable stereosubtleties of macrolactam formation from synthetic seco-cyclosporins. J Am Chem Soc 134:2378-84 |
| Townsend, Steven D; Tan, Zhongping; Dong, Suwei et al. (2012) Advances in proline ligation. J Am Chem Soc 134:3912-6 |
Showing the most recent 10 out of 105 publications
