Preparation of polyethylene glycol‐modified streptokinase with disappearance of binding ability towards anti‐serum and retention of activity

Koide, Atsushi; Suzuki, Suguru; Kobayashi, Seiichi

doi:10.1016/0014-5793(82)80276-7

Cited by 35 publications

(14 citation statements)

References 8 publications

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“…Each derivative possessed only -5% of the reactivity demonstrated by unmodified streptokinase when incubated with antistreptokinase immunoglobulins bound to plastic microtiter wells. These data are consistent with the previous finding of Koide et al (10) that PEG modification substantially decreases the antigenicity of streptokinase. It should be noted that no attempt was made in the present work to assess the immunogenicity of our preparations.…”

Section: Discussionsupporting

confidence: 94%

“…High titers of antibody are present before therapy in some patients or may appear within 2 wk after an initial treatment, complicating long-term therapy (9). Koide et al (10) substantially decreased the reactivity of streptokinase with antibody (antigenicity) by conjugating the protein to polyethylene glycol (PEG; Mr 5,000), a nonantigenic polymer. The PEG was first activated by incubation with cyanuric chloride to form 2-O-methoxypolyethylene glycol-4,6-dichloro-S-triazene.…”

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confidence: 99%

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A nonantigenic covalent streptokinase-polyethylene glycol complex with plasminogen activator function.

Rajagopalan¹,

Gonias²,

Pizzo³

1985

J. Clin. Invest.

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Plasmin activity obtained by incubating streptokinase derivatives with plasminogen also was studied as a function of time with each of the PEG-streptokinase derivatives. By this assay, incubations containing PEG-5-streptokinase and unmodified streptokinase demonstrated comparable activity while reaction mixtures containing PEG-2-streptokinase and PEG4-streptokinase were slightly more active. Streptokinpse incubated with plasminogen at a 1:1 molar ratio was extensively degraded after 30 min whereas PEG-2-streptokinase was resistant to plasmin cleavage. The derivatized proteins were radioiodinated and incubated in plastic microtiter plates that were coated with an immunoglobulin fraction containing antibodies to streptokinase. Binding of the PEG-streptokinase adducts was decreased by >95% compared with unmodified streptokinase. Plasminogen activator complexes were formed by reacting the streptokinases with human plasminogen in vitro and the clearance studied in mice. Radioiodinated plasmin in complex with the PEG-streptokinase adducts cleared at a slower rate than did plasmin complexed with unmodified streptokinase. Catabolism of the protease still occurred by a mechanism that involved reaction with a2-macroglobulin as has been described for nonderivatized streptokinase-plasminogen complex (Gonias, S. L., M. Einarsson, and S. V. Pizzo, 1982, J. Clin. Invest., 70:412-423). When more extensive derivatization procedures were utilized, PEG-2-streptokinase preparations were obtained that further prolonged the clearance of complexed 1251-plasmin;however, these adducts did not uniformly retain comparable activity. It is suggested that PEG-streptokinase complexes with greatly reduced antigenicity may be useful in the treatment of thrombotic disorders.Address reprint requests to Dr. Pizzo.

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Section: Discussionsupporting

confidence: 94%

mentioning

confidence: 99%

A nonantigenic covalent streptokinase-polyethylene glycol complex with plasminogen activator function.

Rajagopalan¹,

Gonias²,

Pizzo³

1985

J. Clin. Invest.

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“…Similarly, PEGylated streptokinase proteins also maintain good activator function but are protected from proteolytic degradation and display decreased antigenicity due to increased steric interference [107,108]. Currently, the only modified streptokinase approved for human use is acylated plasminogenstreptokinase activator complex (APSAC; antistreplase) [93].…”

Section: Second Generation Thrombolytic Therapeutics Based On Streptomentioning

confidence: 99%

The Role of Streptokinase as a Virulence Determinant of Streptococcus pyogenes – Potential for Therapeutic Targeting

McArthur

Cook²,

Venturini³

et al. 2012

CDT

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. (2012). The role of streptokinase as a virulence determinant of streptococcus pyogenes -potential for therapeutic targeting. Current Drug Targets, 13 (3), 297-307. The role of streptokinase as a virulence determinant of streptococcus pyogenes -potential for therapeutic targeting AbstractStreptococcus pyogenes is a major human pathogen responsible for numerous diseases ranging from uncomplicated skin and throat infections to severe, life threatening invasive disease such as necrotising fasciitis and streptococcal toxic shock syndrome. These severe invasive infections progress rapidly and produce high rates of morbidity and mortality despite the implementation of aggressive treatment plans. The activation of plasminogen and the acquisition of plasmin activity at the bacterial cell surface is critical for the invasive pathogenesis of this organism. To facilitate this process, S. pyogenes secrete streptokinase, a potent plasminogen activating protein. Here, we describe the role of streptokinase in invasive pathogenesis and discuss some potentially useful strategies for disruption of streptokinase mediated plasminogen activation which could be employed to treat severe invasive S. pyogenes infections. AbstractStreptococcus pyogenes is a major human pathogen responsible for numerous diseases ranging from uncomplicated skin and throat infections to severe, life threatening invasive disease such as necrotising fasciitis and streptococcal toxic shock syndrome.These severe invasive infections progress rapidly and produce high rates of morbidity and mortality despite the implementation of aggressive treatment plans. The activation of plasminogen and the acquisition of plasmin activity at the bacterial cell surface is critical for the invasive pathogenesis of this organism. To facilitate this process, S. pyogenes secrete streptokinase, a potent plasminogen activating protein.Here, we describe the role of streptokinase in invasive pathogenesis and discuss some potentially useful strategies that disrupt streptokinase mediated plasminogen activation and could be employed to treat severe invasive S. pyogenes infections.3

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“…Based on working mechanism, thrombolytic agents are of two types, one is plasminogen activator which activates plasminogen into active plasmin to degrade fibrin and the other is plasmin like proteins which directly degrade fibrin (Koide et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

Isolation and Screening of Fibrinolytic Enzymes producing Bacterium Strain from Soil Waste

Gopinath¹,

Lingappa²

2016

Int.J.Curr.Microbiol.App.Sci

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Preparation of polyethylene glycol‐modified streptokinase with disappearance of binding ability towards anti‐serum and retention of activity

Cited by 35 publications

References 8 publications

A nonantigenic covalent streptokinase-polyethylene glycol complex with plasminogen activator function.

A nonantigenic covalent streptokinase-polyethylene glycol complex with plasminogen activator function.

The Role of Streptokinase as a Virulence Determinant of Streptococcus pyogenes – Potential for Therapeutic Targeting

Isolation and Screening of Fibrinolytic Enzymes producing Bacterium Strain from Soil Waste

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