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doi:10.1371/journal.ppat.1008932
Federica Giordani, Daniel Paape, Isabel M. Vincent, Andrew W. Pountain, Fernando Fernández-Cortés, Eva Rico, Ning Zhang, Liam J. Morrison, Yvonne Freund, Michael J. Witty, Rosemary Peter, Darren Y. Edwards, Jonathan M. Wilkes, Justin J. J. van der Hooft, Clément Regnault, Kevin D. Read, David Horn, Mark C. Field, Michael P. Barrett
Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs
10.1371/journal.ppat.1008932
http://dx.doi.org/10.1371/journal.ppat.1008932
2020-11-03
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(mode)Tj
2.4945 0 Td
(of)Tj
1.0148 0 Td
(resistance)Tj
4.1329 0 Td
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1.0261 0 Td
(AN11736)Tj
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(animal)Tj
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(trypanosomes.)Tj
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(results)Tj
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3.4129 0 Td
(that)Tj
1.7802 0 Td
(AN11736)Tj
4.0138 0 Td
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(a)Tj
0.652 0 Td
(prodrug)Tj
3.5093 0 Td
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(serine)Tj
2.6136 0 Td
(carboxypeptidases,)Tj
7.7385 0 Td
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(creating)Tj
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(this)Tj
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4.303 0 Td
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(trypanosomes)Tj
5.8223 0 Td
(highly)Tj
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1.0262 0 Td
(AN11736)Tj
4.0138 0 Td
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3.4639 0 Td
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3.5262 0 Td
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(boron)Tj
2.6589 0 Td
(head)Tj
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1.7291 0 Td
(a)Tj
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1 j
1 J
0.0001 w
11.9999 0 0 11.9999 200.012 571.181 cm
BT
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-0.0033 Tc
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0 -1.4976 Td
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1.0677 0 Td
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4.3276 0 Td
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1.0772 0 Td
(AN11736)Tj
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1.063 0 Td
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1.7906 0 Td
()Tj
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(.)Tj
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1.0866 0 Td
( \n )Tj
ET
Q
q
1 j
1 J
0.0001 w
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BT
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-0.004 Tc
1 TL
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4.3823 0 Td
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1.0261 0 Td
(AN11736)Tj
4.0139 0 Td
(was)Tj
1.7007 0 Td
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1.0375 0 Td
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1.0431 0 Td
(\n\r)Tj
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2.6362 0 Td
(and)Tj
/F12 1 Tf
1.7348 0 Td
()Tj
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(.)Tj
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1.0431 0 Td
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4.371 0 Td
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1.1792 0 Td
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4.7395 0 Td
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2.3357 0 Td
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(.)Tj
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1.0488 0 Td
(\n\r)Tj
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2.6362 0 Td
(able)Tj
1.8255 0 Td
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1.0262 0 Td
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2.2507 0 Td
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1.0318 0 Td
(the)Tj
1.474 0 Td
(presence)Tj
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(918)Tj
2.1656 0 Td
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(AN11736)Tj
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2.0353 0 Td
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3.0387 0 Td
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(Fig)Tj
1.8198 0 Td
(1A)Tj
0 g
(\).)Tj
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3.8325 0 Td
(clones)Tj
2.7269 0 Td
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2.0409 0 Td
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3.5829 0 Td
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3.1351 0 Td
(200-fold)Tj
3.5659 0 Td
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Q
q
1 j
1 J
0.0001 w
7.4999 0 0 6.6659 376.724 501.619 cm
BT
/F8 1 Tf
-0.0053 Tc
1 TL
0 0 Td
(R)Tj
ET
Q
q
1 j
1 J
0.0001 w
10 0 0 10 381.373 497.197 cm
BT
/F8 1 Tf
-0.004 Tc
1 TL
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(_A\))Tj
1.7404 0 Td
(and)Tj
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4.337 0 Td
(\(TbOX)Tj
ET
Q
q
1 j
1 J
0.0001 w
7.4999 0 0 6.6659 488.012 501.619 cm
BT
/F8 1 Tf
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1 TL
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(R)Tj
ET
Q
q
1 j
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BT
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(AN11736)Tj
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()Tj
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1.0431 0 Td
(\r\r)Tj
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(,)Tj
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4.5978 0 Td
()Tj
1.0204 0 Td
()Tj
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1.0262 0 Td
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(high-level)Tj
4.1498 0 Td
(resistance.)Tj
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1.0317 0 Td
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(24)Tj
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1.1678 0 Td
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1.474 0 Td
(benzoxaborole,)Tj
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1.3833 0 Td
(subsequent)Tj
4.7055 0 Td
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1.7801 0 Td
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(AN11736)Tj
4.0195 0 Td
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4.1385 0 Td
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0 Tc
1.1792 0 Td
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Q
q
1 j
1 J
0.0001 w
7.4999 0 0 6.6659 418.053 423.666 cm
BT
/F8 1 Tf
-0.0053 Tc
1 TL
0 0 Td
(R)Tj
ET
Q
q
1 j
1 J
0.0001 w
10 0 0 10 422.702 419.187 cm
BT
/F8 1 Tf
-0.004 Tc
1 TL
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(_B\))Tj
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(to)Tj
1.0261 0 Td
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Q
q
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1 J
0.0001 w
7.4999 0 0 6.6659 229.436 410.627 cm
BT
/F8 1 Tf
-0.0053 Tc
1 TL
0 0 Td
(R)Tj
ET
Q
q
1 j
1 J
0.0001 w
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BT
/F8 1 Tf
-0.004 Tc
1 TL
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(_C\))Tj
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(as)Tj
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(line)Tj
1.7065 0 Td
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(Fig)Tj
1.8198 0 Td
(1B)Tj
0 g
(\).)Tj
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1.7859 0 Td
()Tj
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(.)Tj
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1.043 0 Td
(\r\r)Tj
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3.583 0 Td
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3.0274 0 Td
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(the)Tj
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-34.5937 -1.2983 Td
(AN11736)Tj
4.0194 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(S1A)Tj
2.194 0 Td
(Fig)Tj
0 g
(\).)Tj
2.0466 0 Td
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1.7802 0 Td
(resistance)Tj
4.1329 0 Td
(phenotype)Tj
4.439 0 Td
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(these)Tj
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1.6951 0 Td
(stable)Tj
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2.0353 0 Td
(three)Tj
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(the)Tj
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(AN11736)Tj
4.0195 0 Td
(\()Tj
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(S1B)Tj
2.0919 0 Td
(Fig)Tj
0 g
(\).)Tj
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2.8517 0 Td
(but)Tj
1.5533 0 Td
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7.7329 0 Td
()Tj
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(.)Tj
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1.0431 0 Td
(\r\r)Tj
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-32.8476 -1.3039 Td
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3.6849 0 Td
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1.0375 0 Td
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1.8425 0 Td
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(AN11736)Tj
-31.7308 -1.2982 Td
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(S1C)Tj
2.1714 0 Td
(Fig)Tj
0 g
(\).)Tj
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1.7859 0 Td
()Tj
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(.)Tj
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(\r\r)Tj
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4.371 0 Td
(AN11736-resistant)Tj
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3.6906 0 Td
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1.5421 0 Td
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(drugs)Tj
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(currently)Tj
3.8833 0 Td
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(AAT,)Tj
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2.279 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(S1)Tj
1.508 0 Td
(Table)Tj
0 g
(\).)Tj
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-34.1855 -1.2983 Td
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1.2756 0 Td
(cross-resistance)Tj
6.5025 0 Td
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3.0784 0 Td
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(S1)Tj
1.508 0 Td
(Table)Tj
0 g
(\).)Tj
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(cross-resistance)Tj
6.5026 0 Td
(analysis)Tj
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1.0375 0 Td
()Tj
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(.)Tj
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1.0431 0 Td
(\r\r)Tj
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7.7328 0 Td
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(Fig)Tj
1.8199 0 Td
(1C)Tj
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(;)Tj
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(S2)Tj
1.1736 0 Td
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0 g
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1.9956 0 Td
(acoziborole,)Tj
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