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Institutes of Health under award number P20GM109094.
Work in the JCM and KAC labs were partially supported by an
award from the National Institute of Allergy and Infectious
Diseases of the National Institutes of Health (R21AI105656).
Additionally, the Clemson University Honors College and the
Clemson University Creative Inquiry Program are thanked for
their support. The authors thank Artita Sarkar for assistance
with HRMS analysis.
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Brigh*ield#
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Notesꢀandꢀreferencesꢀ
Keywords: African Sleeping Sickness • benzamidobenzoic
BSF#
acid • trypanosomes • Peroxosomal Targeting Sequence •
1
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a.) G. Hide Clin. Microbiol. Rev. 1999, 12, 112-125; b.) C. B.
Beard Emerging Infect. Dis. 2009, 15, 510-511l; c.) M. P. Barrett,
R. J. S. Burchmore, A. Stich, J. O. Lazzari, A. C. Frasch, J. J.
Cazzulo, S. Krishna Lancet 2003, 362, 1469-1480.
Figure 2. Localization of conjugate 13 into the glycosome of BSF T. brucei.
Top row from left to right: DIC image of live procyclic form (PF) T. brucei;
PTS2-mCherry localized into glycosomes of PF T. brucei; Green fluorescent
PTS1-FITC-BABA conjugate 13 localized into glycosomes of PF T. brucei;
merged images of PTS2-mCherry and 13 localized into glycosomes of PF T.
brucei (orange hue indicates overlap). Bottom row from left to right: DIC
image of live bloodstream form (BSF) T. brucei;; PTS2-mCherry localized
into glycosomes of PF T. brucei; Green fluorescent PTS1-FITC-BABA
conjugate 13 localized into glycosomes of BSF T. brucei; merged images of
PTS2-mCherry and 13 localized into glycosomes of BSF T. brucei (orange
hue indicates overlap). Scale bar = 5 µm
2.
E. R. Sharlow, T. A. Lyda, H. C. Dodson, G. Mustata, M. T.
Morris, S. S. Leimgruber, K. H. Lee, Y. Kashiwada, D. Close, J.S.
Lazo, J. C. Morris PLoS Negl. Trop. Dis. 2010 4 (4), e 659.
A. C. Joice, M. T. Harris, E. W. Kahney, H. C. Dodson, A. G.
Maselli, D. C. Whitehead, J. C. Morris, Int. J. Parasitol. Drugs
Drug Resist. 2013, 3, 154-160.
M. Nwagwu, F. R. Opperdoes Acta Trop. 1982, 39, 61-72.
J. W. Chambers, M. L. Fowler, M. T. Morris, J. C. Morris, Mol.
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E. Sharlow, J. E. Golden, H. Dodson, M. Morris, M. Hesser, T.
Lyda, S. Leimgruber, C. E. Schroeder, D. P. Flaherty, W. S.
Weiner, D. Simpson, J. S. Lazo, J. Aube, J. C. Morris
“
(
Identification of inhibitors of Trypanosoma brucei hexokinases”
2010, updated 2011) Probe Report from the NIH Molecular
parasites by means of fluorescence microscopy. We have
confirmed for the first time that PTS1 mediated drug delivery is
possible in trypanosomatids. Further, we suspect that the
PTS1 conjugation strategy for drug delivery described herein
could be applicable to other members of the family, including
T. cruzi and Leishmania major, the causative agents of
Chagas disease and leishmaniasis, respectively. Efforts to
demonstrate the broader efficacy of this strategy with other
trypanosomatids and to develop molecular probes to
understand the cellular mechanisms for PTS1 mediated
uptake in trypanosomes are underway.
Libraries Program. National Center for Biotechnology Information.
H. C. Dodson, M. T. Morris, J. C. Morris J. Biol. Chem. 2011, 286,
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3150-33157.
8.
M. d. L. Milagros Camara, L. A. Bouvier, M. R. Miranda, C. A.
Pereira Exp. Parasitol. 2012, 130, 408-411.
D. Costa-Pinto, L. S. Trindade, D. McMahon-Pratt, Y. M. Traub-
Cseko, Int. J. Parisitol. 2001, 31, 536-543.
9
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10. S. Lin, M. T. Morris, P. C. Ackroyd, J. C. Morris, K. A.
Christensen, Biochemistry 2013, 52, 3629-3637.
1. C. S. Elmore,; D. C. Dean,; R. J. DeVita, D. G. Melillo J. Label
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2. A. C. M. Daugan, O. Mirguet, Y. Lamotte, Quinolinone
Derivatives. U.S. Patent: US 20130345212A1, Dec 26, 2013.
3. D. P. Flaherty, M. T. Harris, C. E. Schroeder, H. Khan, E. W.
Kahney, A. L. Hackler, S. L. Patrick, W. S. Weiner, J. Aubé, E. R.
Sharlow, J. C. Morris, J. E. Golden, Manuscript in preparation
4. Hood, C. A.; Fuentes, G.; Patel; H.; Page, K.; Menakuru, M.; Park,
J. H. J. Pept. Sci. 2008, 14, 97-101.
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Acknowledgements
5. G. B. Fields, R. L. Noble, Int. J. Pept. Protein Res. 1990, 35, 161-
2
14.
The authors would like to thank the Clemson University
Department of Chemistry and Department of Genetics and
Biochemistry for their financial support of this work. Work in
16. B. Raz, M. Iten, Y. Gether-Buhler, R. Kaminsky, R. Brun, Acta
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1
7. H. C. Dodson, T. A. Lyda, J. W. Chambers, M. T. Morris, K. A.
Christensen, J. C. Morris, Exp. Parasitol. 2011, 127, 423-428.
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