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21244441988
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We have recently confirmed the stereochemistry of the first residue, and the geometry of the first amide bond, for PepT1 substrates - see:
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10
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27944447221
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P. D. Bailey C. A. R. Boyd I. D. Collier J. G. George G. L. Kellett D. Meredith K. M. Morgan R. Pettecrew R. A. Price R. G. Pritchard Chem. Commun. 2005 5352
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11
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28444494458
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2 (+2), planar (0), incorrect stereochemistry (-2); factor 7, each aryl ring in pocket (+2), each charge in pocket (-1); factor 8, carboxylate within H-bonding distance of histidine in template (+2)
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P. D. Bailey C. A. R. Boyd I. D. Collier G. L. Kellett D. Meredith K. M. Morgan R. Pettecrew R. A. Price Org. Biomol. Chem. 2005 3 4038
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12
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33645457676
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25
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We found that commercial pharmacophore based modelling was reasonably successful for 'standard' substrates, but the prediction of activity was unreliable for structures outwith the initial training set, with high affinity often attributed to poor substrates
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17
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C. S. Temple A. K. Stewart D. Meredith N. A. Lister K. M. Morgan I. D. Collier R. D. Vaughan-Jones C. A. R. Boyd P. D. Bailey J. R. Bronk J. Biol. Chem. 1998 273 20
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29
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0036510392
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As expected, our quantitative model is a good predictor of the binding of new substrates, as evidenced by the derivatives shown below, which were chosen to probe details of stereochemistry at residue 1 (ref. 7a), and at the 1st peptide bond (ref. 7b).
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S. Theis I. Knütter B. Hartrodt M. Brandsch G. Kottra K. Neubert H. Daniel J. Biol. Chem. 2002 277 7287
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