We recently reported the synthesis, of a potent papain-family cathepsin L-like cysteine protease inhibitor, as new lead compound for the development of new drugs that can be used as antiprotozoal agents. The investigation of its conformational profile is crucial for the in-depth understanding of its biological behaviour. Our careful NMR analysis has been based on the complete and total assignment of 1H, 13C, 15N and 19F signals of the molecule in both CDCl3and CD3OH, which could reproduce in some way a scenario of polar and not polar phases into the biological environment. In this way it has been unveiled a different behaviour of the molecule in polar and apolar media. In CDCl3it is possible to define stable conformational arrangements on the basis of the detected through space contacts, whereas, in CD3OH a greater conformational freedom is envisaged: (a) by the overlap of any of the CH2diastereotopic resonances (unable to distinguish asymmetric molecular sides because of the free rotation about the single bonded chains), (b) by the less definite measured vicinities not consistent with just one conformation and (c) by the evident loss or switching of key intramolecular hydrogen interactions.

NMR Characterization and conformational analysis of a potent papain-family cathepsin L-like cysteine protease inhibitor with different behaviour in polar and apolar media / A. Rotondo, R. Ettari, M. Zappalà, C. De Micheli, E. Rotondo. - In: JOURNAL OF MOLECULAR STRUCTURE. - ISSN 0022-2860. - 1076(2014 Nov 05), pp. 337-343. [10.1016/j.molstruc.2014.07.046]

NMR Characterization and conformational analysis of a potent papain-family cathepsin L-like cysteine protease inhibitor with different behaviour in polar and apolar media

R. Ettari
Secondo
;
C. De Micheli
Penultimo
;
2014

Abstract

We recently reported the synthesis, of a potent papain-family cathepsin L-like cysteine protease inhibitor, as new lead compound for the development of new drugs that can be used as antiprotozoal agents. The investigation of its conformational profile is crucial for the in-depth understanding of its biological behaviour. Our careful NMR analysis has been based on the complete and total assignment of 1H, 13C, 15N and 19F signals of the molecule in both CDCl3and CD3OH, which could reproduce in some way a scenario of polar and not polar phases into the biological environment. In this way it has been unveiled a different behaviour of the molecule in polar and apolar media. In CDCl3it is possible to define stable conformational arrangements on the basis of the detected through space contacts, whereas, in CD3OH a greater conformational freedom is envisaged: (a) by the overlap of any of the CH2diastereotopic resonances (unable to distinguish asymmetric molecular sides because of the free rotation about the single bonded chains), (b) by the less definite measured vicinities not consistent with just one conformation and (c) by the evident loss or switching of key intramolecular hydrogen interactions.
cysteine protease inhibitors; 1H; 13C; 15N NMR; Conformational analysis
Settore CHIM/03 - Chimica Generale e Inorganica
Settore CHIM/08 - Chimica Farmaceutica
   Progettazione e sviluppo di nuovi agenti per il trattamento di malattie parassitarie
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   20124CKP3C_001
5-nov-2014
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/500758
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