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Synthesis of modified fragments of fibrinogen and their effect on the activity of proteolytic enzymes

Abstract

New analogues of the Gly-Pro-Arg and Arg-Gly-Asp fragments of fibrinogen were synthesized: Gly-Pro-Arg-Pro (I), Gly-Pro-Arg-Pro-Met-OMe (II), Gly-Pro-Arg-Pro-Phe (III), Gly-Pro-Arg-Pro-Asp (IV), Gly-Pro-Arg-Pro-Glu (V), and Arg-Asn-Trp-Asp (VI). Their effect on the activity of proteases of various types was studied with the method of lysis of fibrin plates. All the peptides were found to inhibit plasmin activity (by 60–85%) and the γ-subunit of nerve growth factor (by 55–93%). Tetrapeptide (VI) proved to be an effective inhibitor of tissue activator of plasminogen and the γ-subunit of nerve growth factor (by 96 and 93%, respectively). The peptides exerted practically no effect on the activity of urokinase and moderately inhibited the activity of streptokinase [(III), IV), and (VI)], papain [(I), (II), IV), and (VI)], subtilisin [(V) and (VI)], α-chymotrypsin [(III), (V), and VI)], and Bacillus subtilis metalloprotease (VI). They inhibit trypsin [except for (I) and (III)] when applied on fibrin plates at a concentration of 1 × 10−2 M, while, at the concentration of 1 × 10−3 M, (I) and (II) induced an increase in proteolytic activity by 35 and 47%, respectively.

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Abbreviations

DCC:

N,N′-dicyclohexylcarbodiimide

HOBt:

1-hydroxybenzotriazole

NGF:

nerve growth factor

NSu:

N-succinimidyl

Pcp:

pentachlorophenyl

Pfp:

pentafluorophenyl

TAP:

tissue activator of plasminogen

TEA:

triethylamine

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Correspondence to V. P. Martinovich.

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Original Russian Text © V.N. Nikandrov, N.S. Pyzhova, V.P. Golubovich, O.V. Mel’nik, V.P. Martinovich, 2006, published in Bioorganicheskaya Khimiya, 2006, Vol. 32, No. 2, pp. 144–150.

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Nikandrov, V.N., Pyzhova, N.S., Golubovich, V.P. et al. Synthesis of modified fragments of fibrinogen and their effect on the activity of proteolytic enzymes. Russ J Bioorg Chem 32, 129–135 (2006). https://doi.org/10.1134/S106816200602004X

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  • DOI: https://doi.org/10.1134/S106816200602004X

Key words

  • fragments of fibrinogen
  • synthesis of analogues
  • effect on activity of proteases