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Although the degradation of several cytoskeleton proteins such as α-fodrin, actin, and spectrin has been used to gauge the activity of calpain, there is no compelling evidence that any of these proteins is the natural substrate. The high catalytic promiscuity of calpain is manifested in the data in reference [4], in which 49 identified substrates with 106 cleavage sites are compiled. As the authors point out, the actual number of calpain substrates is higher, as evidenced by the growing number of recently published papers that report the hydrolysis of natural proteins catalyzed by calpain.
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33746627845
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note
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As is the case for the various substrates of calpain, there is an increasing number of papers that report the participation of calpain in different physiological and metabolic processes. Therefore, it is not clear which (if any) is the precise physiological role for this protease. However, some the most studied processes include cytoskeleton remodeling, apoptosis and necrosis, cell cycle, and cell motility. For some reviews, see reference [3].
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33746583365
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The decision to use the sec-butyl group at C3 was taken on the basis that the four diastereomers of 2-amino-3-methyl-butanoic acid are readily available.
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24
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33746657839
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13C NMR, MS, IR) and analytical (C, H, N, ± 0.30%) methods.
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26
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0042379984
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33746598400
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note
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These peptides were prepared by standard methodology by using N-Boc and methyl ester protection. The coupling step was realized with the combination of 1-hydroxybenzotriazole (HOBT), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) and 4-(dimethylamino)pyridine (DMAP).
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33746655590
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50 values.
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35
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0030576333
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36
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33746632307
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note
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2+-mediated activation of calpain.
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