Structural basis for the potent calpain inhibitory activity of peptidyl α-ketoacids

Journal of Medicinal Chemistry

Volumn 51, Issue 14, 2008, Pages 4346-4350

  Donkor, Isaac O ^a   Assefa, Haregewein ^a,b   Liu, Jiuyu ^a  

^a UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^b Transcept Pharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALPAIN; CALPAIN 1; ESTER DERIVATIVE; N (2,2 DIPHENYLACETYL)LECUCYL 2 OXO 3 AMINO 4 PHENYLBUTANOIC ACID; N (3,3 DIPHENYLPROPIONYL)LEUCYL 2 OXO 3 AMINO 4 PHENYLBUTANOIC ACID; N (9 FLUORENEACETYL)LEUCYL 2 OXO 3 AMINO 4 PHENYLBUTANOIC ACID; OXOACID; PEPTIDE DERIVATIVE;

AMINO TERMINAL SEQUENCE; ARTICLE; DIASTEREOISOMER; DRUG POTENCY; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME INHIBITION; HYDROGEN BOND; MOLECULAR DOCKING; MOLECULAR INTERACTION; STRUCTURE ACTIVITY RELATION;

ACIDS; CALPAIN; CYSTEINE PROTEINASE INHIBITORS; HYDROGEN BONDING; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PEPTIDES; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION;

EID: 47749097114     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm800182c     Document Type: Article

References (14)

1. Suzuki, K.; Sorimachi, H.; Yoshizawa, T.; Kinbara, K.; Ishiura, S. Calpain: novel family members, activation, and physiologic function. Biol Chem. 1995, 376, 523-529.
2. Croall, D. E.; DeMartino, G. N. Calcium-activated neutral protease (calpain) system: structure, function, and regulation. Physiol. Rev. 1991, 71, 813-847.
3. 2+ exchanger in excitotoxicity. Cell 2005, 120, 275-285.
4. Zatz, A.; Starling, A. Calpains and disease. N. Engl. J. Med. 2005, 352, 2413-2423.
5. Donkor, I. O. A survey of calpain inhibitors. Curr. Med. Chem. 2000, 12, 1171-1188.
6. Neffe, A. T.; Abell, A. D. Developments in the design and synthesis of calpain inhibitors. Curr. Opin. Drug Discovery Dev. 2005, 6, 684-700.
7. Takahashi, K. In Intracellular Calcium-Dependent Proteolysis; Mellgren, R. L., Murachi, T. , Ed.; CRC Press: Boca Raton, FL, 1990; pp 55-74.
8. 2+ switch aligns the active site of calpain. Cell 2002, 108, 649-660.
9. Cuerrier, D.; Moldoveanu, T.; Inoue, J.; Davies, P. L.; Campbell, R. L. Calpain inhibition by alpha-ketoamide and cyclic hemiacetal inhibitors revealed by X-ray crystallography. Biochemistry 2006, 45, 7446-7452.
10. Harbeson, S. L.; Abelleira, S. M.; Akiyama, A.; Barrett, R., III.; Carroll, R. M.; Straub, J. A.; Tkacz, J. N.; Wu, C.; Musso, G. F. Stereospecific synthesis of peptidyl alpha-keto amides as inhibitors of calpain. J. Med. Chem. 1994, 37, 2918-2929.
11. Lescop, C.; Herzner, H.; Siendt, H.; Bolliger, R.; Hennebohle, M.; Weyermann, P.; Briguet, A.; Courdier-Fruh, I.; Erb, M.; Foster, M.; Meier, T.; Magyar, J. P.; von Sprecher, A. Novel cell-penetrating alpha-keto-amide calpain inhibitors as potential treatment for muscular dystrophy. Bioorg. Med. Chem. Lett. 2005, 15, 5176-5181.
12. Li, Z.; Paul, G. S.; Golubski, Z. E.; Hori, H.; Tehrani, K.; Foreman, J. E.; Eveleth, D. D.; Bartus, R. T.; Powers, J. C. Peptide alpha-keto ester, alpha-keto amide, and alpha-keto acid inhibitors of calpains and other cysteine proteases. J. Med. Chem. 1993, 36, 3472-3480.
13. Angelastro, M. R.; Marquart, A. L.; Mehdi, S.; Koehl, J. R.; Vaz, P. B.; Peet, N. P. The synthesis of ketomethylene pseudopeptide analogues of dipeptide aldehyde inhibitors of calpain. Bioorg. Med. Chem. Lett. 1999, 9, 139-140.
14. i. Biochem. J. 1972, 129, 197-202.