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PubMedDate not supplied

[Cystatin C as a measure of glomerular filtration in patients with kidney transplants].

INTRODUCTION: Assessment of renal function is of great importance in clinical medicine, especially in renal transplant patients requiring frequent controls of renal function. Therefore, continuous efforts have been made in searching precise and simple method for determination of glomerular filtration rate (GFR). Serum level of cystatin C (CyC), protein of low molecular weight, has been proposed as measure of GFR, but the data of its value in renal transplant patients are scarce [8-10]. PURPOSE: The aim of this study was to compare the serum levels of low molecular weight proteins CyC and beta 2-microglobulin (beta 2-MG) with creatinine clearance, as well known measure of GFR, in renal transplant patients and control group of patients with different renal disease. PATIENTS AND METHODS: The study included 36 patients divided into two groups. Group 1: 20 renal transplant patients (12 men and 8 women) aged between 22 and 63 (40.4 +/- 10.1) years with creatinine clearance from 7.1 to 77.7 ml/min. Group 2: 16 controls (5 men and 11 women) with various renal diseases, aged between 24 and 63 (41.5 +/- 12.5) years with creatinine clearance from 60.5 to 116.8 ml/min. N Latex Cystatin C and beta 2-microglobulin for the Behring Nephelometer System was used in this study. Creatinine was determined with Jaffe-reaction in serum and urine. RESULTS: In renal transplant patients as well as in control group of patients the significant correlation between creatinine clearance and reciprocal values of the serum CyC (rt = 0.828; pt < 0.001; rc = 0.603; pc < 0.05) and reciprocal values of the serum beta 2-MG levels (rt = 0.791; pt < 0.001; rc = 0.627; pc < 0.05) was found (Graph 1). There was a slightly better correlation between creatinine clearance and reciprocal values of the serum CyC than the one between creatinine clearance and reciprocal values of the serum beta 2-MG without statistical significance in renal transplant patients. There was no difference in correlation coefficients between both low molecular weight proteins and creatinine clearance in Group 2. The correlation coefficient between serum CyC and beta 2-MG was r = 0.839 (p < 0.001) in renal transplant patients and r = 0.835 (p < 0.05) in control group. There were no significant differences in correlation coefficients between reciprocal values of serum CyC and creatinine clearance (p = 0.2043) as well as reciprocal values of serum beta 2-MG and creatinine clearance (p = 0.3717) between Group 1 and Group 2. DISCUSSION: In renal transplant patients rapid assessment of graft function is necessary. This allows early recognition of rejection as well as differential diagnosis of different renal graft disorders. Study of Risch and co [16] suggested that serum CyC was very good marker for GFR in renal transplant patients which was confirmed by the other authors too [20-22]. During inflammatory process or other pathological conditions, especially during acute rejection or infections. CyC also provided precise assessment of GFR while creatinine clearance varied dramatically [16]. Serum concentration of beta 2-MG, another low molecular weight protein, also depends both on its production rate and the GFR [5, 19]. Its production is dramatically different in patients with infections [5] as well as while immunosuppressive drugs are used [16]. Therefore, beta 2-MG is impractical as GFR marker in patients with renal transplants. So, serum CyC was considered as better marker for GFR than beta 2-MG and creatinine clearance in renal transplant patients with different complications [16]. In this study serum CyC was slightly better marker for GFR than beta 2-MG, without statistical significance (Graph 1). Renal transplant patients, however, were in the stable condition at the time of the study. CONCLUSION: Serum CyC was moderately better marker of GFR than beta 2-MG in renal transplant patients when they were in the stable condition. Serum CyC and beta 2-MG were the same markers of GFR in control group of patients with various renal diseases. There was no significant difference in correlation coefficients between reciprocal values of the serum CyC and creatinine clearance (p = 0.2043) as well as reciprocal values of the serum beta 2-MG levels and creatinine clearance (p = 0.3717) between two examined groups of patients. The studies on renal transplant patients with acute graft rejection or infections are warranted.

Adult↗
PubMed2006

A genome-wide linkage scan for genes controlling variation in renal function estimated by serum cystatin C levels in extended families with type 2 diabetes.

We performed a variance components linkage analysis of renal function, measured as glomerular filtration rate (GFR), in 63 extended families with multiple members with type 2 diabetes. GFR was estimated from serum concentrations of cystatin C and creatinine in 406 diabetic and 428 nondiabetic relatives. Results for cystatin C were summarized because they are superior to creatinine results. GFR aggregates in families with significant heritability (h(2)) in diabetic (h(2) = 0.45, P < 1 x 10(-5)) and nondiabetic (h(2) = 0.36, P < 1 x 10(-3)) relatives. Genetic correlation (r(G) = 0.35) between the GFR of diabetic and nondiabetic relatives was less than one (P = 0.01), suggesting that genes controlling GFR variation in these groups are different. Linkage results supported this interpretation. In diabetic relatives, linkage was strong on chromosome 2q (logarithm of odds [LOD] = 4.1) and suggestive on 10q (LOD = 3.1) and 18p (LOD = 2.2). In nondiabetic relatives, linkage was suggestive on 3q (LOD = 2.2) and 11p (LOD = 2.1). When diabetic and nondiabetic relatives were combined, strong evidence for linkage was found only on 7p (LOD = 4.0). In conclusion, partially distinct sets of genes control GFR variation in relatives with and without diabetes on chromosome 2q, possibly on 10q and 18p in the former, and on 7p in both. None of these genes overlaps with genes controlling variation in urinary albumin excretion.

Adult↗
PubMed1992

Cystatin C based peptidyl diazomethanes as cysteine proteinase inhibitors: influence of the peptidyl chain length.

The peptidyl diazomethanes Cbz-Gly-CHN2, Boc-Val-Gly-CHN2, H-Leu-Val-Gly-CHN2, Cbz-Leu-Val-Gly-CHN2 and Cbz-Arg-Leu-Val-Gly-CHN2, with peptidyl portions modelled after the proposed cysteine proteinase interacting N-terminal segment of human cystatin C, were synthesized. Their efficiency as cysteine proteinase inhibitors was tested against papain, human cathepsin B and bovine cathepsin B. All, except Cbz-Gly-CHN2, were found to be irreversible inhibitors of the tested enzymes. Each addition of an amino acid residue to their peptidyl portions resulted in an increased inhibition rate of all three enzymes. These data suggest that the arginyl residue of the tetrapeptidyl diazomethane, and also the corresponding arginyl residue in native cystatin C, interact with a S4 substrate pocket subsite of both papain and cathepsin B. The most efficient inhibitor, Cbz-Arg-Leu-Val-Gly-CHN2, inhibited papain and cathepsin B with rate constants of the same order of magnitude as those for L-3-carboxy-trans-2,3-epoxypropionyl-leucylamido-(4-guanidin o)butane (E-64). The high water-solubility of Cbz-Arg-Leu-Val-Gly-CHN2 allowing it to be dissolved to molar concentrations without use of non-physiological additives, makes it suitable for in vitro and in vivo cysteine proteinase inhibition studies.

Amino Acid Sequence↗
PubMed2000

Comparison of cystatin C versus creatinine for detection of mild renal failure.

AIM: Serum cystatin C (SCyst) has been proposed as a novel indicator of GFR. PATIENTS AND METHODS: We compared SCyst, serum creatinine (SCreat) and Cockcroft and Gault's estimated clearance (CCG) using inulin clearance (Cin) as gold standard. 140 subjects (161 samples; aged 39 +/- 14; male/female: 79/82) underwent simultaneous measurements. RESULTS: A highly significant correlation r = 0.70, 0.74, 0.77 (p < 0.0001) was found between 1/SCyst, 1/SCreat, C(CG), respectively, and Cin. Receiver-operating characteristic (ROC) analysis was performed on SCyst, SCreat and C(CG) using a Cin cut-off of 90 ml/min/1.73 m2. Best fit for SCyst was 0.90 mg/l with a sensitivity of 75% and a specificity of 92%. The area under the ROC curve was not significantly greater for SCreat or C(CG) than for SCyst (p = 0.91,0.13, respectively). When relationship between Cin and SCyst was plotted, experimental data deviated from the theoretical model, suggesting that cystatin C may not be solely filtered. Additional patients were selected in our database on the basis of discordant SCreat/GFR values: false negative (n = 46 samples, 31 patients) and false positive (n = 16 samples, 9 patients). In this highly selected subgroup, 38% of the SCreat false positive had normal SCyst values and 48% of the false negative SCreat had abnormally elevated SCyst. CONCLUSION: This study suggests that SCyst is not more sensitive than SCreat or C(CG) for detecting renal failure, however, SCyst could be proposed as a confirmatory test for patients with elevated SCreat.

Adolescent↗
PubMed2000

[Levels of cystatin C, activity of antipapain and antitrypsin in plasma of patients with diabetes mellitus type 2].

In plasma of 72 patients with diabetes mellitus type 2, cystatin C concentration, the antipapain as well as antitrypsin activities were determined. Statistically significant increase of levels of all the examined parameters (higher for inhibitors of cysteine proteases) was found in comparison to healthy persons. When considering types of vascular complications, the highest concentration of cystatin C and the strongest positive correlation with antipapain activity was found in the group of patients with microangiopathy. It might be connected with glomerular damages. Only antipapain as well as antitrypsin activities showed significant correlation with glycaemic control as measurement by glycated haemoglobin concentration.

Adult↗
PubMed2002

Cystatin C: an improved estimator of glomerular filtration rate?

BACKGROUND: Glomerular filtration rate (GFR) is routinely assessed by measuring the concentrations of endogenous serum markers such as blood urea nitrogen and serum creatinine (SCr). Although widely used, these endogenous markers are not ideal and do not perform optimally in certain clinical settings. The purpose of this review is to critically review the potential utility of cystatin C (CysC), especially in patient populations in which CysC may have an advantage over routinely used endogenous markers of GFR. APPROACH: In a narrative approach, we extensively review publications, primarily from the last 5 years, that address the development of methods to measure CysC, reference intervals, and the diagnostic accuracy of CysC to assess GFR. Between June 2000 and September 2001 Medline was searched using "cystatin c" as a textword, and articles that examined >75 individuals (except for renal transplant studies) and/or used accepted "gold standards" for assessing GFR were selected for inclusion. A total of 17 studies are reviewed that provide reference interval data for several populations. A total of 24 studies make conclusions about the utility of CysC vs SCr and/or creatinine clearance, with 20 providing data on the sensitivity and specificity of CysC for detecting impaired GFR. These publications are organized into subgroups that deal with specific patient populations or clinical situations. CONTENT: This review focuses on two areas: (a) the evolution of immunoassays used to determine the concentration of CysC in serum, their analytic sensitivity, and reference intervals; and (b) the diagnostic performance of CysC against other renal markers in the general population and in specific subpopulations of patients. SUMMARY: Studies of reference intervals for CysC overwhelmingly demonstrated that CysC values in blood are independent of age and sex. Of the 24 studies that examined clinical utility, 15 concluded that CysC is superior to SCr, whereas 9 concluded that CysC is equivalent but provides no advantage. Summary ROC plot analysis of 20 studies that provide sensitivity and specificity data strongly suggests that CysC will be superior to SCr for detecting impaired GFR. Taken together, it is clear that CysC performs at least as well as SCr in the population at large and that it is likely to be superior to SCr in specific patient populations.

Biomarkers↗
PubMed2006

[Could cystatine C replace creatinine as a market of glomerular filtration rate?].

Measurement of glomerular filtartion rate (GFR) is crucial for the detection and follow-up of an early renal impairment. Inulin clearance or radio-isotopes are the gold standard but they cannot be used routinely. Serum creatinine and creatinine clearance are the most widely used, but they lack sensibility to detect an early renal impairment and in cases of obesity, malnutrition or advanced age. Looking for a more reliable marker is necessary and cystatin C seems to be interesting. This molecule is constantly produced by nucleated cells, then freely filtrated and catabolized in the proximal tube. Clinical studies showed that cystatin C might be a more reliable marker of GFR in determined groups of patients. Moreover this molecule may have an other interest as a predictive risk factor or mortality, especially for cardiovascular events.

Biomarkers↗
PubMed2006

Comparison of estimated glomerular filtration rates from serum creatinine and cystatin C in patients with impaired creatinine production.

Determination of the glomerular filtration rate (GFR) is important for the drug dosage adjustment and clinical management of patients. The aim of our study was the comparison of estimated GFR values from serum creatinine (eGFRcreatinine) and cystatin C (eGFRcystatin C) in patients with impaired creatinine production. A total of 564 serum samples from patients with kidney disease (n=179), liver (n=71) and kidney (n=182) transplants, critically ill patients (n=82) and healthy subjects (n=50) were analyzed for serum creatinine and cystatin C. The creatinine production rate (CPR) was significantly lower in the different groups of patients than in the control group (p<0.001). A negative correlation was found between the eGFRcreatinine/eGFRcystatin C ratio and CPR (r= -0.964, p<0.001). For CPR higher than 800 mg/24h both procedures for estimating the GFR classified values higher and lower than 60 mL/min with an acceptable agreement; however, for CPR less than 800 mg/24h the eGFRcreatinine led to false negatives in a high number of cases with eGFRcystatin C <60 mL/min.

Adult↗
PubMed1991

[A case of lobar cerebral hemorrhage with low concentration of CSF cystatin C].

A 49-year-old male was admitted to our hospital because of severe headache and dizziness which had occurred suddenly one day before admission. There was no past history contributory to cerebral hemorrhage but was family history of cerebrovascular accidents in his father and brother. Neurological examination revealed left homonymous hemianopsia, mild left hemiparesis, and left side hemi-neglect in simultaneous stimuli on bilateral extremities. Laboratory data including peripheral blood cells, coagulation tests, and serum chemistry were unremarkable. Brain CT and MRI demonstrated large lobar hematoma in the right parieto-occipito-temporal region. Cystatin C level in the CSF samples taken on the 39th and 59 th days (38 and 27 ng/ml respectively) were low, compared with the normal value (greater than 100 ng/ml). These findings suggest that the lobar cerebral hemorrhage of the present case might have been caused by cerebral amyloid angiopathy with cystatin C deposits.

Amyloidosis↗
PubMedDate not supplied

Cystatin C: a new marker of biocompatibility or a good marker for the redistribution of LMW proteins during hemodialysis?

The mechanism(s) behind the larger relative increase of Plasma beta 2 microglobulin (P-beta 2m) than that of Plasma albumin (P-alb) during Cuprophan hemodialysis is disputed. To elucidate this phenomenon P-alb, P-beta 2m (MW 11,800) and Plasma cystatin (P-cC; MW 13,000) an inhibitor of cystein proteinases, were determined before and after a Cuprophan or polysulphone hemodialysis (4-7 hr, QB 200 ml/min) in 30 stable regular dialysis treatment (RDT) patients. Body weight (BW) decreased by 2.5 +/- 1.4% (mean +/- SD). P-alb, P-beta 2m and P-cC increased by 11.4 +/- 14.8%, 15.4 +/- 11.5%, and 22.1 +/- 14.3%, respectively, during Cuprophan dialysis. The relative increase of P-cC was larger than that of P-beta 2m (P less than 0.05) and that of P-alb (P less than 0.02). During polysulphone dialysis BW decreased by 4.1 +/- 1.8%. P-alb, P-beta 2m, and P-cC increased almost equally by 28.1 +/- 18, 26.5 +/- 19.2, and 26.8 +/- 14.4%, respectively. These results are hard to interpret. Is the increase in P-cC a new marker of biocompatibility or does it reflect the true shift of low molecular weight (LMW) proteins between the interstitial and the plasma volume during hemodialysis better than P-beta 2m? In vitro studies indicate that small amounts of both Serum beta 2m (S-beta 2m) and Serum cystatin C (S-cC) are adsorbed to or sieved through the Cuprophan membrane, findings which render the kinetics of LMW proteins during hemodialysis still more complex.

Biocompatible Materials↗
PubMed1988

Purification of the cystatin C-like inhibitors from urine of nephropathic rats.

Two cysteine proteinase inhibitors of the cystatin C type have been purified from urine of sodium chromate-treated rats. Both strongly inhibit papain as well as rat liver cathepsin L (Ki less than 10(-11) M) whereas rat liver cathepsins B and H are inhibited to a lesser extent. They differ by their apparent molecular mass of 17 kDa and 22 kDa and by their isoelectric point greater than or equal to 9.5 and 7.7 respectively. These two molecules share complete immunochemical identity and are precipitated by antibodies directed against human cystatin C but not by anti rat thiostatin and anti rat H-kininogen antibodies. They are also found in large amounts in seminal vesicles where they represent most of the cysteine proteinase inhibitory capacity.

Animals↗
PubMed1987

Novel monocyte-like properties of microglial/astroglial cells. Constitutive secretion of lysozyme and cystatin-C.

Evidence implicates cells belonging to the mononuclear phagocytic system (MPS) in the development of some forms of amyloidosis (10, 22). Whether or not the MPS is involved in central nervous system amyloidosis is not known. As a first step to address this issue, microglial and astroglial cells isolated from mouse brains were cultured and characterized as to the properties they may share with other members of the MPS. It was shown by light and electron microscopy that both cell types phagocytose latex particles, but that only microglial cells engulf immunoglobulin sensitized erythrocytes. By means of immunohistochemical, immunofluorescence, and immunoblotting techniques, it was established that the cells contain and secrete lysozyme as well as the proteinase inhibitor cystatin-C (-gamma trace). Cystatin-C was distributed in the cytoplasm and the nucleus and was strikingly associated with filaments and bundles of fibrils. Another enzyme, commonly used to distinguish cells belonging to the MPS, is alpha-naphthyl butyrate esterase. Shortly after their isolation, only the microglial cells were positive, but on continued culturing, increasing numbers of astroglial cells became positive for alpha-naphthyl butyrate esterase. By day 22, almost all of the cells were positive. Freshly isolated cells were negative for the monocyte-specific antigen Mac-1. However, after 4 days, cells with the morphology of microglia had become positive, whereas astroglia failed to exhibit this antigen with up to 22 days in culture. Thus, both astroglia and microglia have properties in common with cells of the MPS which may be useful for future studies. However, on fresh isolation only microglia were indistinguishable from monocytes for all features tested.

Animals↗
PubMed1996

Inhibition of bovine cathepsins L and S by stefins and cystatins.

Inhibition of bovine cathepsins L and S by bovine stefin B, human stefins A and B and cystatin C was studied under pseudo-first-order conditions by continuous fluorimetric assay. All inhibitors formed very tight complexes with the enzymes (Ki < or = 29 pM). The binding was reversible (kdiss = 0.52 - 16.7 x 10(-4) s-1) and very fast (kass = 2.8 - 6.2 x 10(7) M-1 S-1). Cystatin C was the strongest inhibitor of the enzymes, but the affinity was too tight to be measured accurately by this method. Consistently weaker inhibition of cathepsin S by all the stefins is apparent due mainly to the higher dissociation rate constants.

Animals↗
PubMedDate not supplied

Recapitulation of germ cell- and pituitary-specific expression with 1.6 kb of the cystatin-related epididymal spermatogenic (Cres) gene promoter in transgenic mice.

The Cres (cystatin-related epididymal spermatogenic) gene encodes the defining member of a new subgroup within the family 2 cystatins of cysteine protease inhibitors. Cres expression is highly tissue- and cell-specific, with messenger RNA (mRNA) present in the testicular round/elongating spermatids, proximal caput epididymal epithelium, gonadotroph cells in the anterior pituitary gland, and corpus luteum of the ovary. To begin to elucidate the molecular mechanisms controlling the tissue- and cell-specific expression of the Cres gene, transgenic mice were generated containing 1.6 kilobases (kb) of the mouse Cres promoter linked to the bacterial chloramphenicol acetyltransferase (CAT) reporter gene. A CAT enzyme-linked immunosorbent assay detected CAT protein in the testis, epididymis, isolated cauda epididymal spermatozoa, and anterior pituitary gland from mice heterozygous and homozygous for the transgene. However, reverse transcription (RT)-PCR did not detect CAT mRNA in any regions of the epididymis, suggesting that the CAT protein detected in the epididymis was from spermatozoa. RT-PCR also did not detect CAT mRNA in the ovary. RT-PCR analysis of the testes from mice of different postnatal ages showed CAT mRNA first detected at day 22, which correlated with the first appearance of Cres mRNA and with the presence of round spermatids. These studies demonstrate that 1.6 kb of Cres promoter contains the DNA elements necessary for germ cell and pituitary gland-specific expression but lacks critical sequences necessary for expression in the epididymis and ovary.

Animals↗
PubMed1999

Full-length cDNA of human cathepsin F predicts the presence of a cystatin domain at the N-terminus of the cysteine protease zymogen.

A novel human cDNA encoding a cysteine protease of the papain family named cathepsin F is reported. The mature part of the predicted protease precursor displays between 26% and 42% identity to other human cysteine proteases while the proregion is unique by means of length and sequence. The very long proregion of the cathepsin F precursor (251 amino acid residues) can be divided into three regions: a C-terminal domain similar to the pro-segment of cathepsin L-like enzymes, a 50 residue flexible linker peptide, and an N-terminal domain predicted to adopt a cystatin-like fold. Cathepsin F would therefore be the first cysteine protease zymogen containing a cystatin-like domain.

Amino Acid Sequence↗
PubMed1993

The structures of native phosphorylated chicken cystatin and of a recombinant unphosphorylated variant in solution.

The solution structures of the phosphorylated form of native chicken cystatin and the recombinant variant AEF-S1M-M29I-M89L were determined by 2D, 3D and 4D-NMR. The structures turn out to be very similar, despite the substitutions and the phosphorylation of the wild-type. Their dominant feature is a five-stranded beta-sheet, which is wrapped around a five-turn alpha-helix, as shown by X-ray crystallographic studies of wild-type chicken cystatin. However, the NMR analysis shows that the second helix observed in the crystal is not present in solution. The phosphorylation occurs at S80, which is located in a flexible region. For this reason, very few effects on the structure are observed. Comparison of structures of the unphosphorylated variant and the wild-type shows small effects on H84 which is located in the supposed recognition site of the serine kinase. This recognition site appears to be well structured as a large loop-containing bulge of the beta-sheet. The N termini of both mutants, which contribute to a large extent to the binding to the proteinase, are very flexible. A loop structure involving the residues L7 to A10 as found in related inhibitors, such as in the kininogen domains 2 and 3, is not sufficiently populated to be observed.

Amino Acid Sequence↗
PubMed1996

Transgenic rice established to express corn cystatin exhibits strong inhibitory activity against insect gut proteinases.

Corn cystatin (CC), a phytocystatin, shows a wide inhibitory spectrum against various cysteine proteinases. We produced transgenic rice plants by introducing CC cDNA under CaMV 35S promoter as a first step to obtain a rice plant with insecticidal activity. This attempt was based on the observation that many insect pests, especially Coleoptera, have cysteine proteinases, probably digestive enzymes, and also that oryzacystatin, an intrinsic rice cystatin, shows a narrow inhibition spectrum and is present in ordinary rice seeds in insufficient amounts to inhibit the cysteine proteinases of rice insect pests. The transgenic rice plants generated contained high levels of CC mRNA and CC protein in both seeds and leaves, the CC protein content of the seed reaching ca. 2% of the total heat soluble protein. We also recovered CC activity from seeds and found that the CC fraction efficiently inhibited both papain and cathepsin H, whereas the corresponding fraction from non-transformed rice seeds showed much lower or undetectable inhibitory activities against these cysteine proteinases. Furthermore, CC prepared from transgenic rice plants showed potent inhibitory activity against proteinases that occur in the gut of the insect pest, Sitophilus zeamais.

Animals↗
PubMed1995

Conserved cystatin segments as models for designing specific substrates and inhibitors of cysteine proteinases.

Peptide segments derived from consensus sequences of the inhibitory site of cystatins, the natural inhibitors of cysteine proteinases, were used to develop new substrates and inhibitors of papain and rat liver cathepsins B, H, and L. Papain hydrolyzed Abz-QVVAGA-EDDnp and Abz-LVGGA-EDDnp at about the same rate, with specificity constants in the 10(7) M-1 sec-1 range; cathepsin L also hydrolyzes both substrates with specificity constants in the 10(5) M-1 sec-1 range due to lower k(cat) values, with the Km's being identical to those with papain. Only Abz-LVGGA-EDDnp was rapidly hydrolyzed by cathepsin B, and to a lesser extent by cathepsin H. Peptide substrates that alternate these two building blocks (LVGGQVVAGAPWK and QVVAGALVGGAPWK) discriminate the activities of cathepsins B and L and papain. Cathepsin L was highly selective for cleavage at the G-G bond of the LVGG fragment in both peptides. Papain and cathepsin B cleaved either the LVGG fragment or the QVVAG fragment, depending on their position within the peptide. While papain was more specific for the segment located C-terminally, cathepsin B was specific for that in N-terminal position. Peptidyl diazomethylketone inhibitors based on these two sequences also reacted differently with papain and cathepsins. GlcA-QVVA-CHN2 was a potent inhibitor of papain and reacted with papain 60 times more rapidly (k + 0 = 1,100,000 M-1 sec-1) than with cathepsin L, and 220 times more rapidly than with cathepsin B. Cathepsins B and L were preferentially inhibited by Z-RLVG-CHN2. Thus cystatin-derived peptides provide a valuable frame-work for designing sensitive, selective substrates and inhibitors of cysteine proteinases.

Amino Acid Sequence↗