Inhibition of aspartic proteinases by propart peptides of human procathepsin D and chicken pepsinogen

Fusek, Martin; Mareš, Michael; Vagner, Josef; Vobůrka, Zdeněk; Baudyš, Miroslav

doi:10.1016/0014-5793(91)80040-a

Cited by 39 publications

(38 citation statements)

References 15 publications

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“…The inhibitory effect is demonstrated by a propeptide split off during procathepsin D autoactivation [73,94,95] and by respective fragments of its structure [96]. Alpha2-macroglobulin is an endogenous plasma inhibitor of this protease [97,98].…”

Section: Activators and Inhibitorsmentioning

confidence: 99%

Human cathepsin D.

Minarowska

Gacko²,

Karwowska³

et al. 2008

Folia Histochem Cytobiol.

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Section: Activators and Inhibitorsmentioning

confidence: 99%

Human cathepsin D.

Minarowska

Gacko²,

Karwowska³

et al. 2008

Folia Histochem Cytobiol.

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“…Intact pro-parts of human procathepsin D and chicken pepsinogen inhibit most aspartic proteinases with hi in the nanomolar range and with significant pH dependence [40]. Screening of synthetic fragments of the pro-part of prorenin identified two shorter peptides inhibiting renin: the peptide lOP-20P and the C-terminal peptide 32P-43P [41].…”

Section: The Ph Of Physiological Activationmentioning

confidence: 99%

Multiple functions of pro‐parts of aspartic proteinase zymogens

et al. 1994

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The importance of aspartic proteinases in human pathophysiology continues to initiate extensive research. With burgeoning information on their biological functions and structures, the traditional view of the role of activation peptides of aspartic proteinases solely as inhibitors of the active site is changing. These peptide segments, or pro-parts, am deemed important for correct folding, targeting, and control of the activation of aspartic proteinase zymogens. Consequently, the primary structures of pro-parts reflect these functions. We discuss guidelines for formation of hypotheses derived from comparing the physiological function of aspartic proteinases and sequences of their pro-parts.

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“…The proregions of these proteinases are essential for such physiological functions as intracellular trafficking, correct folding of the enzyme during maturation, and inhibition of the mature enzyme [1][2][3][4][5]. The inhibition of proteinases by their respective proregions is a rather specific process [6,7], and this relationship can be used to develop a new generation of specific peptide inhibitors. The cysteine proteinases of the papain family are particularly appropriate targets for such a strategy, since no specific synthetic substrates and inhibitors are available to follow the activity of individual members.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of cathepsin B by its propeptide: Use of overlapping peptides to identify a critical segment

et al. 1996

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Ten overlapping 15-mer peptides (peptidyl amides) spanning the proregion of rat cathepsin B (residues lp-60p) were constructed to identify minimal segments having inhibitory activity towards the mature enzyme, that could be used to develop a new generation of peptide-derived inhibitors specifically targeting the active site of the corresponding proteinase. Three synthetic peptides, containing the pentapeptide Leu-CysGly-Thr-Val (residues 41p-45p) in their sequence, inhibited cathepsin B with Ki values in the micromolar range. Alkylation of the thiol group of Cys-42p of peptide PB8 (36p-50p) resulted in its rapid proteolytic degradation, suggesting that this residue is essential for inhibition. The inhibition constant was slightly improved (Kt = 2 ltM) using a longer peptide (26p-50p) which was completely resistant to cleavage even after a prolonged incubation. Alkylation of its cysteinyl residue also resulted in rapid cleavage of the peptide chain. Peptides derived from the rat cathepsin B prosequence also inhibited human cathepsin B with similar Kl values. Unlike rat cathepsin B, which cleaves peptide PB8 at the G47p-G48p bond after prolonged incubation, the human enzyme cleaved both PB8 and PBll at the Lys-40p-Leu41p bond, in agreement with the different kinetic properties of these two proteinases. New probes with improved specificity for cysteine proteinases may therefore be designed based on the sequences of their propeptides.

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Inhibition of aspartic proteinases by propart peptides of human procathepsin D and chicken pepsinogen

Cited by 39 publications

References 15 publications

Human cathepsin D.

Human cathepsin D.

Multiple functions of pro‐parts of aspartic proteinase zymogens

Inhibition of cathepsin B by its propeptide: Use of overlapping peptides to identify a critical segment

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