The C‐terminal binding domain of hirullin P18

FEBS Letters

Mao, Simon J.T.¹  Yates, Mark T.¹  Krstenansky, John L.¹  Owen, Thomas J.¹ 

[1] Merrell Dow Research Institute, 2110 E. Galbraith Road, Cincinnati, Ohio 45215, USA

关键词: Hirullin P18;    Hirudin;    Synthetic peptide;    Thrombin;    AAA;    amino acid analysis;    Boc;    t-butoxycarbonyl;    Bzl;    benzyl;    Chx;    cyclohexyl;    2-C1Z;    2-chlorobenzyloxycarbonyl;    DCC;    N;    N'-dicyclohexylcarbodiimide;    DCM;    dichloromethane;    DMF;    N;    N-dimethylformainide;    FAB-MS;    fast-atom bombardment mass spectrometry;    HOBT;    1-hydroxybenzotriazole;    HP18;    N α-acetylhirullin P1840–61;    HPLC;    high performance liquid chromatography;    Hyp;    4-hydroxy-l-proline;    Pip;    l-pipecolic acid;    pNA;    p-nitroanilide;    Tos;    tosyl;   

DOI  :  10.1016/0014-5793(90)81208-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Hirullin P18 is a 61-amino acid hirudin-related protein having potent antithrombin activity. Similar to hirudin, it contains a highly acidic C-terminus, but has a significantly different sequence from any other known hirudin variant. The present study demonstrates that the C-terminal fragment acetyl-hirullin P18_40–61 possesses an antithrombin potency similar to that of acetyl-desulfatohirudin_45–65. Additionally, like the hirudin fragment analog, it inhibits fibrin-clot formation by binding to a non-catalytic site on thrombin. Sequential shortening of the hirullin P18 C-terminal fragment demonstrates the critical nature of Phe⁵¹, which corresponds to the important Phe⁵⁶ residue of hirudin. Although the sequences of hirullin P18_54–61 and hirudin_59–65 have substantial differences, the C-terminal functional domain represented by hirullin P18_50–61 appears to be comparable to hirudin_55–65 in terms of its functional role in antithrombin activity.

【 授权许可】

Unknown