scholarly journals The Discovery of Synthetic Proteolytic Peptide

2018 ◽  
Author(s):  
Rina Nakamura ◽  
Motomi Konishi ◽  
Masanari Taniguchi ◽  
Yusuke Hatakawa ◽  
Toshifumi Akizawa
Keyword(s):  
Amino Acids ◽  
Serine Protease ◽  
Proteolytic Activity ◽  
Synthetic Peptide ◽  
Synthetic Peptides ◽  
Serine Protease Inhibitor ◽  
Small Peptides ◽  
Physiological Conditions ◽  
Proteolytic Activities ◽  
Catalytic Peptides

After screening nearly 1000 synthetic peptides, a synthetic peptide termed JAL-AK22 (KYEGHWYPEKPYKGSGFRCIHI) derived from the BoxA domain in Tob1 protein was found to activate both unfolded and folded proMMP-7. In addition, JAL-AK22 showed auto-proteolytic activity. Interestingly, the smaller derivative of JAL-AK22 termed JAL-TA9 (YKGSGFRMI) also possessed auto-proteolytic activity and cleaved 2 fragment peptides (MMP18-33 and MMP18-40) derived from the prodomain of proMMP-7 under physiological conditions. These proteolytic activities were inhibited by AEBSF, a serine protease inhibitor. Our results demonstrate that a small synthetic peptide consisting of only 9 amino acids has serine protease-like activity and activates proMMP-7 by cleaving the prodomain region. We thus propose calling small peptides possessing with protease-like activity Catalytides (catalytic peptides). We expect that our findings will stimulate the development of novel Catalytides and related applications.

scholarly journals The Discovery of Synthetic Proteolytic Peptide

2018 ◽  
Author(s):  
Rina Nakamura ◽  
Aya Kojima ◽  
Motomi Konishi ◽  
Masanari Taniguchi ◽  
Yusuke Hatakawa ◽  
...  
Keyword(s):  
Amino Acids ◽  
Serine Protease ◽  
Proteolytic Activity ◽  
Synthetic Peptide ◽  
Synthetic Peptides ◽  
Serine Protease Inhibitor ◽  
Small Peptides ◽  
Physiological Conditions ◽  
Proteolytic Activities ◽  
Catalytic Peptides

After screening nearly 1000 synthetic peptides, a synthetic peptide termed JAL-AK22 (KYEGHWYPEKPYKGSGFRCIHI) derived from the BoxA domain in Tob1 protein was found to activate both unfolded and folded proMMP-7. In addition, JAL-AK22 showed auto-proteolytic activity. Interestingly, the smaller derivative of JAL-AK22 termed JAL-TA9 (YKGSGFRMI) also possessed auto-proteolytic activity and cleaved 2 fragment peptides (MMP18-33 and MMP18-40) derived from the prodomain of proMMP-7 under physiological conditions. These proteolytic activities were inhibited by AEBSF, a serine protease inhibitor. Our results demonstrate that a small synthetic peptide consisting of only 9 amino acids has serine protease-like activity and activates proMMP-7 by cleaving the prodomain region. We thus propose calling small peptides possessing with protease-like activity Catalytides (catalytic peptides). We expect that our findings will stimulate the development of novel Catalytides and related applications.

scholarly journals Selective Recognition of Amino Acids and Peptides by Small Supramolecular Receptors

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 106
Author(s):  
Joana N. Martins ◽  
João Carlos Lima ◽  
Nuno Basílio
Keyword(s):  
Amino Acids ◽  
Selective Recognition ◽  
Great Promise ◽  
Macrocyclic Compounds ◽  
Synthetic Receptors ◽  
Small Peptides ◽  
Molecular Imprinted Polymers ◽  
Polymeric Systems ◽  
Physiological Conditions ◽  
Level Information

To this day, the recognition and high affinity binding of biomolecules in water by synthetic receptors remains challenging, while the necessity for systems for their sensing, transport and modulation persists. This problematic is prevalent for the recognition of peptides, which not only have key roles in many biochemical pathways, as well as having pharmacological and biotechnological applications, but also frequently serve as models for the study of proteins. Taking inspiration in nature and on the interactions that occur between several receptors and peptide sequences, many researchers have developed and applied a variety of different synthetic receptors, as is the case of macrocyclic compounds, molecular imprinted polymers, organometallic cages, among others, to bind amino acids, small peptides and proteins. In this critical review, we present and discuss selected examples of synthetic receptors for amino acids and peptides, with a greater focus on supramolecular receptors, which show great promise for the selective recognition of these biomolecules in physiological conditions. We decided to focus preferentially on small synthetic receptors (leaving out of this review high molecular weight polymeric systems) for which more detailed and accurate molecular level information regarding the main structural and thermodynamic features of the receptor biomolecule assemblies is available.

scholarly journals The conjugation of nonsteroidal anti-inflammatory drugs (NSAID) to small peptides for generating multifunctional supramolecular nanofibers/hydrogels

2013 ◽  
Vol 9 ◽  
pp. 908-917 ◽  
Author(s):  
Jiayang Li ◽  
Yi Kuang ◽  
Junfeng Shi ◽  
Yuan Gao ◽  
Jie Zhou ◽  
...  
Keyword(s):  
Amino Acids ◽  
Critical Concentration ◽  
Therapeutic Agents ◽  
Multiple Roles ◽  
Small Peptides ◽  
Covalent Linkage ◽  
Physiological Conditions ◽  
Racemic Ibuprofen ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Here we report supramolecular hydrogelators made of nonsteroidal anti-inflammatory drugs (NSAID) and small peptides. The covalent linkage of Phe–Phe and NSAIDs results in conjugates that self-assemble in water to form molecular nanofibers as the matrices of hydrogels. When the NSAID is naproxen (1), the resultant hydrogelator 1a forms a hydrogel at a critical concentration (cgc) of 0.2 wt % at pH 7.0. Hydrogelator 1a, also acting as a general motif, enables enzymatic hydrogelation in which the precursor turns into a hydrogelator upon hydrolysis catalyzed by a phosphatase at physiological conditions. The conjugates of Phe–Phe with other NSAIDs, such as (R)-flurbiprofen (2), racemic flurbiprofen (3), and racemic ibuprofen (4), are able to form molecular hydrogels, except in the case of aspirin (5). After the conjugation with the small peptides, NSAIDs exhibit improved selectivity to their targets. In addition, the peptides made of D-amino acids help preserve the activities of NSAIDs. Besides demonstrating that common NSAIDs are excellent candidates to promote aromatic–aromatic interaction in water to form hydrogels, this work contributes to the development of functional molecules that have dual or multiple roles and ultimately may lead to new molecular hydrogels of therapeutic agents for topical use.

Diversity in growth and protein degradation by dairy relevant lactic acid bacteria species in reconstituted whey

2012 ◽  
Vol 79 (2) ◽  
pp. 201-208 ◽  
Author(s):  
Micaela Pescuma ◽  
Elvira M. Hébert ◽  
Elena Bru ◽  
Graciela Font de Valdez ◽  
Fernanda Mozzi
Keyword(s):  
Amino Acids ◽  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Protein Degradation ◽  
Proteolytic Activity ◽  
Starter Culture ◽  
Whey Proteins ◽  
Principal Component ◽  
Fermented Foods ◽  
Small Peptides

The high nutritional value of whey makes it an interesting substrate for the development of fermented foods. The aim of this work was to evaluate the growth and proteolytic activity of sixty-four strains of lactic acid bacteria in whey to further formulate a starter culture for the development of fermented whey-based beverages. Fermentations were performed at 37°C for 24 h in 10 and 16% (w/v) reconstituted whey powder. Cultivable populations, pH, and proteolytic activity (o-phthaldialdehyde test) were determined at 6 and 24 h incubation. Hydrolysis of whey proteins was analysed by Tricine SDS-PAGE. A principal component analysis (PCA) was applied to evaluate the behaviour of strains. Forty-six percent of the strains grew between 1 and 2 Δlog CFU/ml while 19% grew less than 0·9 Δlog CFU/ml in both reconstituted whey solutions. Regarding the proteolytic activity, most of the lactobacilli released amino acids and small peptides during the first 6 h incubation while streptococci consumed the amino acids initially present in whey to sustain growth. Whey proteins were degraded by the studied strains although to different extents. Special attention was paid to the main allergenic whey protein, β-lactoglobulin, which was degraded the most byLactobacillus acidophilusCRL 636 andLb. delbrueckiisubsp.bulgaricusCRL 656. The strain variability observed and the PCA applied in this study allowed selecting appropriate strains able to improve the nutritional characteristics (through amino group release and protein degradation) and storage (decrease in pH) of whey.

scholarly journals Induction of passive Heymann nephritis with antibodies specific for a synthetic peptide derived from the receptor-associated protein.

1996 ◽  
Vol 183 (5) ◽  
pp. 2007-2015 ◽  
Author(s):  
D Kerjaschki ◽  
R Ullrich ◽  
M Exner ◽  
R A Orlando ◽  
M G Farquhar
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Synthetic Peptide ◽  
Synthetic Peptides ◽  
Target Sequence ◽  
Receptor Associated Protein ◽  
Binding Domains ◽  
Heymann Nephritis ◽  
Experimental Rat Model

Passive Heymann nephritis (pHN) is an experimental rat model for human membranous glomerulopathy. In pHN, the formation of subepithelial immune deposits (ID) involves as antigenic targets the membrane glycoprotein gp330/megalin and the 44-kD receptor-associated protein (RAP). A single binding site for ID- inducing antibodies (Abs) was previously mapped to the 86 NH2-terminal amino acids of RAP (RAP1-86). To further narrow this epitope, Abs eluted from the glomeruli were immunoblotted on membranes that were loaded with overlapping synthetic peptides representing the amino acid sequence of RAP (SPOTs system). Two adjacent Ab-binding domains with the sequences PVRLAF, (amino acids 39-44) and HSD-LKIQE (amino acids 46-53), which were separated by a single L residue at amino acid 45, were detected. Rabbit Abs raised against synthetic peptides containing these domains individually (P31-44 and P46-53) failed to procedure glomerular IDs. By contrast, Abs raised against a larger composite peptide (P31-53) induced IDs within 3d that were firmly cross linked to the glomerular basement membrane. These data suggest that Ab binding in vivo depends on the conformation of the antigenic target sequence that is preserved in the synthetic peptide P31-53, which covers the entire Ab-binding domain of RAP but not in its subdomains, P31-44 and P46-53. Collectively, these results locate the sole ID-inducing epitope of RAP to amino acids 39-53.

scholarly journals Proteinase activity in latex of three plants of the family Euphorbiaceae

2014 ◽  
Vol 50 (3) ◽  
pp. 559-565 ◽  
Author(s):  
Andréa Michel Sobottka ◽  
Fabiana Tonial ◽  
Sonja Sytwala ◽  
Matthias Melzig
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Proteolytic Activity ◽  
Specific Activity ◽  
Serine Protease Inhibitor ◽  
Polyacrylamide Gels ◽  
Protein Activity ◽  
Sds Page ◽  
The Family ◽  
Molecular Masses

In the family of Euphorbiaceae,the genera Euphorbia and Sapium are known to contain essentially latex-bearing species. In the present study, the latex of Euphorbia selloi(Klotzsch & Garcke) Boiss., Euphorbia papillosa A.St.-Hil., and Sapium glandulosum (L.) Morong, plants native from Brazil, were examined concerning proteolytic activity. All studied species have proteins with significant proteolytic activity and E. papillosa has the greatest specific activity. Aiming to verify the type of protease present, an assay with different inhibitors was performed. In the three tested plants, the proteolytic activity was significantly inhibited by a serine protease inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride (AEBSF). Using techniques of electrophoresis with polyacrylamide gels (SDS-PAGE), the subunits of proteins were separated according to their molecular masses, and the protein activity was visually detected by zymography.

Discoordinate hormonal and ontogenetic regulation of four rat serpin genes

1992 ◽  
Vol 262 (5) ◽  
pp. C1144-C1148 ◽  
Author(s):  
S. J. Schwarzenberg ◽  
J. B. Yoon ◽  
S. Seelig ◽  
C. J. Potter ◽  
S. A. Berry
Keyword(s):  
Growth Hormone ◽  
Protease Inhibitor ◽  
Serine Protease ◽  
Serine Protease Inhibitor ◽  
Age Group ◽  
Serum Growth Hormone ◽  
Physiological Conditions ◽  
Specific Mrnas ◽  
Alpha 1 Antitrypsin ◽  
Inhibitor Genes

To understand the roles of four highly homologous rat hepatic serine protease inhibitor genes (Spi 2.1, Spi 2.2, Spi 2.3, and alpha 1-antitrypsin), we measured the hepatic content of their specific mRNAs under several physiological conditions. Spi 2.1 and 2.3 mRNAs, which are regulated by growth hormone, paralleled serum growth hormone levels developmentally. Only Spi 2.1 mRNA decreased with starvation, while Spi 2.2, 2.3, and alpha 1-antitrypsin mRNAs did not change. Despite the close homology of the Spi genes to mouse contrapsin, which is regulated by testosterone, none of the serine protease inhibitor mRNAs examined here was dependent on androgens for expression. Spi 2.2 mRNA displayed a unique ontogenetic regulation, with a rise in hepatic content at day 19 to levels five times that of any other age group. These studies confirm the importance of growth hormone in the regulation of Spi 2.1 and 2.3 mRNAs and suggest that Spi 2.2 mRNA may be regulated by metabolic alterations occurring in the weaning period.

scholarly journals Identification of an immunosuppressive epitope of type II collagen that confers protection against collagen-induced arthritis.

1989 ◽  
Vol 170 (6) ◽  
pp. 1999-2010 ◽  
Author(s):  
L K Myers ◽  
J M Stuart ◽  
J M Seyer ◽  
A H Kang
Keyword(s):  
Amino Acids ◽  
Antibody Response ◽  
Synthetic Peptide ◽  
Synthetic Peptides ◽  
Cyanogen Bromide ◽  
Type I Collagen ◽  
Type Ii Collagen ◽  
Type I ◽  
Type Ii ◽  
Collagen Induced Arthritis

We have previously reported that collagen-induced arthritis can be suppressed by intravenous injection of native type II (CII) but not type I collagen. We have now identified denatured fragments of CII capable of suppressing collagen-induced arthritis and inducing tolerance. Purified CII was cleaved with cyanogen bromide (CB), and the major resulting peptides were isolated. Female DBA/1 mice were administered OVA, native CII, or one of the CB peptides, intravenously, before immunization with native CII, 6 wk after immunization, mice tolerized with CII and CB11 had a markedly lower incidence of arthritis compared with controls. There was a correlation between the overall antibody response and the incidence of arthritis. In addition, animals tolerized with either CII or CB11 had a decreased antibody response not only to CII, but also to each of the other CB peptides tested. To identify the epitope involved in suppression of arthritis, five synthetic peptides, 21-26 amino acids in length, corresponding to selected regions of CB11, were generated. Each of the peptides was injected intravenously into mice before immunization. Only one of these, CB11 122-147, was capable of suppressing arthritis. In addition, mice given the synthetic peptide CB11 122-147 neonatally were suppressed for arthritis and antibody responsiveness when immunized with CII at 8 wk of age. Thus, we have identified CB11 122-147 as an epitope of CII important in induction of tolerance and suppression of disease. Further experiments narrowing down the pivotal amino acids for the immunogenicity of this epitope and the role this epitope plays in induction and regulation of disease will enhance our understanding of how the immune response to collagen affects autoimmune arthritis.

A basal-defined medium for the study of proteolytic activity of Serratia marcescens

1999 ◽  
Vol 45 (1) ◽  
pp. 88-91 ◽  
Author(s):  
Bruno J Bromke ◽  
Elaine Venuti
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Serratia Marcescens ◽  
Proteolytic Activity ◽  
Growth Parameters ◽  
Basal Medium ◽  
Defined Medium ◽  
Logarithmic Phase ◽  
Proteolytic Activities ◽  
Basal Salts

A simple defined basal medium is presented for the study of proteolytic activity, induction and repression, and protease purification with Serratia marcescens. Since the medium contains no protein, it does not interfere with or present artifact to protein assays, column chromatography, or electrophoresis. The medium consists of the basal salts and buffer medium of Bromke and Hammel (1979) plus a carbon-energy source such as glycerol, calcium chloride for the cation requirement for protease activity, and an amino acid, preferably leucine. Growth parameters and proteolytic activities are presented for unsupplemented medium and for the medium supplemented with each of 18 amino acids. Unsupplemented medium completes the logarithmic phase in 12.5 h of incubation and has a constitutive level of proteolytic activity. Supplementation with any amino acid, except cysteine and tryptophan, increases significantly the proteolytic activity, but has a varied effect on growth parameters.Key words: Serratia marcescens, growth, proteolytic activity, amino acids, leucine.

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