Proteolytic Degradation of the Aα Chain of Human Fibrinogen

1979 ◽  
Author(s):  
J.A. Conkie ◽  
Isobel D. Walker ◽  
J.F. Davidson
Keyword(s):  
Molecular Weight ◽  
Amino Acid ◽  
Amino Acid Composition ◽  
Proteolytic Degradation ◽  
Composition Analysis ◽  
Terminal Part ◽  
High Solubility ◽  
Human Fibrinogen

On plasmin degradation of human fibrinogen, a number of polypeptides are released from the COOH-terminal part of the Aα chain. One of these fragments has been previously named by us as Aα-RA(26,000). By comparison of its molecular weight and amino acid composition analysis, this fragment is similar to the fragments A,H and Hi2-Met. Aα-RA(26,00O) appears to be derived from a precursor polypeptide of Mw 44,000, while in vitro and in vivo activation of the plasma fibrinolytic system also gives rise to an Aα-related antigen which is immunologically similar to the 44,000 MW polypeptide. On immunodiffusion with antiserum to the carboxymethylated Aα chain, Aα-RA(26 000) revealed a reaction of identity with the high solubility fibrinogen fraction 1-9 (major NH2-terminal Aα remnant, MW 34,000) and a reaction of non-identity with the ancrod-proauced COOH-terminal Aα polypeptides (MW 27,000-31,000). These immunodiffusion results provide evidence that the sequence of bond cleavages in the Aα chain leading to the formaron of fibrinogen 1-9 is different from that leading to the formation of Aα-Ra (126,000).

“In vivo” amplification of biological activity of tetragastrin by amino acid hydroxamates

1984 ◽  
Vol 4 (12) ◽  
pp. 1009-1015 ◽  
Author(s):  
J. P. Bali ◽  
H. Mattras ◽  
A. Previero ◽  
M. A. Coletti-Previero
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Aromatic Amino Acid ◽  
Aminopeptidase Activity ◽  
Proteolytic Degradation ◽  
Short Peptides ◽  
Rat Blood ◽  
Active Peptides

Rat blood was shown to contain an aminopeptidase which rapidly hydrolyses short peptides containing an aromatic amino acid as N-terminal residue. Using tetragastrin (Trp-Met-Asp-PheNH 2) as substrate, we showed that some amino acid hydroxamates inhibit rat aminopeptidase activity ‘in vitro’ in the following order: HTrpNHOH > HPheNHOH ≫ HAIaNHOH. The same hydroxamates markedly enhanced the biological activity of tetragastrin ‘in vivo’. The amplification of the secretory effect, correlated with the amount of the hydroxamate used, strongly suggests that these compounds can stabilize a number of active peptides in vivo by inhibiting their proteolytic degradation.

Predicting Interactions Between Pathogen and Human Proteins Based on the Relation Between Sequence Length and Amino Acid Composition

2021 ◽  
Vol 16 ◽  
Author(s):  
Saud Alguwaizani ◽  
Shulei Ren ◽  
De-Shuang Huang ◽  
Kyungsook Han
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Yersinia Pestis ◽  
Acid Composition ◽  
Sequence Length ◽  
Support Vector ◽  
Human Ppis ◽  
Svm Model

Aim: Both bacterial infection and viral infection involve a large number of protein-protein interactions (PPIs) between a pathogen and its target host. Background: So far, many computational methods have focused on predicting PPIs within the same species rather than PPIs across different species. Methods: From the extensive analysis of PPIs between Yersinia pestis bacteria and humans, we recently discovered an interesting relation; a linear relation between amino acid composition and sequence length was observed in many proteins involved in PPIs. We have built a support vector machine (SVM) model, which predicts PPIs between human and bacteria using two feature types derived from the relation. The two feature types used in the SVM are the amino acid composition group (AACG) and the difference in amino acid composition between host and pathogen proteins. Result: The SVM model achieved high performance in predicting bacteria-human PPIs. The model showed an accuracy of 96%, sensitivity of 94%, and specificity of 98% in predicting PPIs between humans and Yersinia pestis, in which there is a strong relation between amino acid composition and sequence length. The SVM model was also tested in predicting PPIs between human and viruses, which include Ebola, HCV, and SARSCoV-2, and showed a good performance. Conclusion: The feature types identified in our study are simple yet powerful in predicting pathogen-human PPIs. Although preliminary, our method will be useful for finding unknown target host proteins or pathogen proteins and designing in vitro or in vivo experiments.

scholarly journals Scrambled Prion Domains Form Prions and Amyloid

2004 ◽  
Vol 24 (16) ◽  
pp. 7206-7213 ◽  
Author(s):  
Eric D. Ross ◽  
Ulrich Baxa ◽  
Reed B. Wickner
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Sequence Composition ◽  
Amino Terminal ◽  
Rich Domain ◽  
The Many ◽  
Necessary And Sufficient

ABSTRACT The [URE3] prion of Saccharomyces cerevisiae is a self-propagating amyloid form of Ure2p. The amino-terminal prion domain of Ure2p is necessary and sufficient for prion formation and has a high glutamine (Q) and asparagine (N) content. Such Q/N-rich domains are found in two other yeast prion proteins, Sup35p and Rnq1p, although none of the many other yeast Q/N-rich domain proteins have yet been found to be prions. To examine the role of amino acid sequence composition in prion formation, we used Ure2p as a model system and generated five Ure2p variants in which the order of the amino acids in the prion domain was randomly shuffled while keeping the amino acid composition and C-terminal domain unchanged. Surprisingly, all five formed prions in vivo, with a range of frequencies and stabilities, and the prion domains of all five readily formed amyloid fibers in vitro. Although it is unclear whether other amyloid-forming proteins would be equally resistant to scrambling, this result demonstrates that [URE3] formation is driven primarily by amino acid composition, largely independent of primary sequence.

The Action of Brinase in Vitro and in Vivo

1975 ◽  
Author(s):  
P. J. Gaffney ◽  
K. Lord ◽  
R. D. Thornes
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Size Range ◽  
Degradation Products ◽  
Molecular Size ◽  
Human Fibrinogen ◽  
Rate Limiting Step ◽  
Rate Limiting

Brinase (an extract of Aspergillus Oryzae) was shown to rapidly digest human fibrinogen in vitro to aggregable degradation products with a molecular size range of 310,000 to 230,000 the latter fragments being more slowly digested to core fragments, Dbr and Ebr. The fibrinogen polypeptide chain susceptibility to Brinase attack was in the order Aα, γ, Bβ, Lysis of the Bβ chain seems to be the rate limiting step in the conversion of the high molecular weight fragments (MW 310,000–230,000) to the core fragments Dbr and Ebr. The conservation of NH2 terminal Tyrosine during fibrinogen digestion and the very transient existence of D dimer fragments during totally crosslinked fibrin lysis suggest that the carboxy end of the γ chain is prone to Brinase attack. The crosslinked α chains of fibrin, while resistant to plasmin, are vigorously digested by Brinase. The plasma of cancer patients being treated with Brinase contained degraded fibrinogen (lacking intact Aα chains) and their aggregates. These aggregates contained some crosslinked γ chains (γ-γ dimers) suggesting that Brinase in vivo exorcises both a lytic and coagulant effect. Thrombin mediated clots in all the plasmas examined contained no crosslinked α chains. Positive plasma ethanol gelation tests can be explained by the presence of the aggregable high molecular weight fragments observed during the in vitro lysis of fibrinogen by Brinase.

Alphastatin, a 24–amino acid fragment of human fibrinogen, is a potent new inhibitor of activated endothelial cells in vitro and in vivo

Blood ◽  
2004 ◽  
Vol 103 (2) ◽  
pp. 601-606 ◽  
Author(s):  
Carolyn A. Staton ◽  
Nicola J. Brown ◽  
Gary R. Rodgers ◽  
Kevin P. Corke ◽  
Simon Tazzyman ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Amino Acid ◽  
Growth Factor ◽  
Detectable Effect ◽  
Tubule Formation ◽  
Human Fibrinogen ◽  
Amino Acid Peptide ◽  
Normal Tissues

Abstract Angiogenesis, the development of new blood vessels from existing vasculature, is crucial for the development and metastasis of solid tumors. Here, we show for the first time that a 24–amino acid peptide derived from the amino terminus of the alpha chain of human fibrinogen (termed “alphastatin”) has potent antiangiogenic properties, inhibiting both the migration and tubule formation of human dermal microvascular endothelial cells in response to vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) in vitro. Moreover, alphastatin markedly inhibits the growth of tumors in a syngeneic murine model. Tumors from mice receiving daily injections of alphastatin for 12 days exhibited large areas of intravascular disruption and thrombosis with substantial cellular necrosis. Importantly, alphastatin administration had no detectable effect on vessels in such normal tissues as liver, lungs, and kidney. Taken together, these data indicate that alphastatin is a potent new antiangiogenic agent in vitro and antivascular agent in vivo.

scholarly journals A Promiscuous Prion: Efficient Induction of [URE3] Prion Formation by Heterologous Prion Domains

Genetics ◽  
2009 ◽  
Vol 183 (3) ◽  
pp. 929-940 ◽  
Author(s):  
Carley D. Ross ◽  
Blake R. McCarty ◽  
Michael Hamilton ◽  
Asa Ben-Hur ◽  
Eric D. Ross
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
De Novo ◽  
Amyloid Formation ◽  
Wild Type ◽  
Amyloid Aggregates ◽  
Efficient Induction

The [URE3] and [PSI+] prions are the infections amyloid forms of the Saccharomyces cerevisiae proteins Ure2p and Sup35p, respectively. Randomizing the order of the amino acids in the Ure2 and Sup35 prion domains while retaining amino acid composition does not block prion formation, indicating that amino acid composition, not primary sequence, is the predominant feature driving [URE3] and [PSI+] formation. Here we show that Ure2p promiscuously interacts with various compositionally similar proteins to influence [URE3] levels. Overexpression of scrambled Ure2p prion domains efficiently increases de novo formation of wild-type [URE3] in vivo. In vitro, amyloid aggregates of the scrambled prion domains efficiently seed wild-type Ure2p amyloid formation, suggesting that the wild-type and scrambled prion domains can directly interact to seed prion formation. To test whether interactions between Ure2p and naturally occurring yeast proteins could similarly affect [URE3] formation, we identified yeast proteins with domains that are compositionally similar to the Ure2p prion domain. Remarkably, all but one of these domains were also able to efficiently increase [URE3] formation. These results suggest that a wide variety of proteins could potentially affect [URE3] formation.

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

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