Structural Biology and Protein Engineering of Thrombolytics

J 2019

Structural Biology and Protein Engineering of Thrombolytics

MIČAN, Jan, Martin TOUL, David BEDNÁŘ a Jiří DAMBORSKÝ

Základní údaje

Originální název

Structural Biology and Protein Engineering of Thrombolytics

Název česky

Strukturní biologie a proteinové inženýrství trombolytik

Autoři

MIČAN, Jan (203 Česká republika, domácí), Martin TOUL (203 Česká republika, domácí), David BEDNÁŘ (203 Česká republika, garant, domácí) a Jiří DAMBORSKÝ (203 Česká republika, domácí)

Vydání

Computational and Structural Biology Journal, Amsterdam, Elsevier, 2019, 2001-0370

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Full Text

Impakt faktor

Impact factor: 6.018

Kód RIV

RIV/00216224:14310/19:00108351

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1016/j.csbj.2019.06.023

UT WoS

000504205700091

Klíčová slova anglicky

Fibrinolysis; Staphylokinase; Streptokinase; Thrombolysis; Tissue plasminogen activator; Urokinase

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 2. 2023 22:19, Mgr. Michaela Hylsová, Ph.D.

Anotace

V originále

Myocardial infarction and ischemic stroke are the most frequent causes of death or disability worldwide. Due to their ability to dissolve blood clots, the thrombolytics are frequently used for their treatment. Improving the effectiveness of thrombolytics for clinical uses is of great interest. The knowledge of the multiple roles of the endogenous thrombolytics and the fibrinolytic system grows continuously. The effects of thrombolytics on the alteration of the nervous system and the regulation of the cell migration offer promising novel uses for treating neurodegenerative disorders or targeting cancer metastasis. However, secondary activities of thrombolytics may lead to life-threatening side-effects such as intracranial bleeding and neurotoxicity. Here we provide a structural biology perspective on various thrombolytic enzymes and their key properties: (i) effectiveness of clot lysis, (ii) affinity and specificity towards fibrin, (iii) biological half-life, (iv) mechanisms of activation/inhibition, and (v) risks of side effects. This information needs to be carefully considered while establishing protein engineering strategies aiming at the development of novel thrombolytics. Current trends and perspectives are discussed, including the screening for novel enzymes and small molecules, the enhancement of fibrin specificity by protein engineering, the suppression of interactions with native receptors, liposomal encapsulation and targeted release, the application of adjuvants, and the development of improved production systems.

Návaznosti

EF16_013/0001761, projekt VaV

Název: RECETOX RI

LM2015047, projekt VaV

Název: Česká národní infrastruktura pro biologická data (Akronym: ELIXIR-CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Česká národní infrastruktura pro biologická data

LM2015085, projekt VaV

Název: CERIT Scientific Cloud (Akronym: CERIT-SC)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CERIT Scientific Cloud

TN01000013, projekt VaV

Název: Personalizovaná medicína - diagnostika a terapie

Investor: Technologická agentura ČR, Personalizovaná medicína - diagnostika a terapie

Citovat

MIČAN, Jan, Martin TOUL, David BEDNÁŘ a Jiří DAMBORSKÝ. Structural Biology and Protein Engineering of Thrombolytics. Computational and Structural Biology Journal. Amsterdam: Elsevier, 2019, roč. 17, č. 2019, s. 917-938. ISSN 2001-0370. Dostupné z: https://dx.doi.org/10.1016/j.csbj.2019.06.023.

@article{1545297,
   author = {Mičan, Jan and Toul, Martin and Bednář, David and Damborský, Jiří},
   article_location = {Amsterdam},
   article_number = {2019},
   doi = {http://dx.doi.org/10.1016/j.csbj.2019.06.023},
   keywords = {Fibrinolysis; Staphylokinase; Streptokinase; Thrombolysis; Tissue plasminogen activator; Urokinase},
   language = {eng},
   issn = {2001-0370},
   journal = {Computational and Structural Biology Journal},
   title = {Structural Biology and Protein Engineering of Thrombolytics},
   url = {https://www.sciencedirect.com/science/article/pii/S2001037019302065},
   volume = {17},
   year = {2019}
}

TY  - JOUR
ID  - 1545297
AU  - Mičan, Jan - Toul, Martin - Bednář, David - Damborský, Jiří
PY  - 2019
TI  - Structural Biology and Protein Engineering of Thrombolytics
JF  - Computational and Structural Biology Journal
VL  - 17
IS  - 2019
SP  - 917-938
EP  - 917-938
PB  - Elsevier
SN  - 20010370
KW  - Fibrinolysis
KW  - Staphylokinase
KW  - Streptokinase
KW  - Thrombolysis
KW  - Tissue plasminogen activator
KW  - Urokinase
UR  - https://www.sciencedirect.com/science/article/pii/S2001037019302065
L2  - https://www.sciencedirect.com/science/article/pii/S2001037019302065
N2  - Myocardial infarction and ischemic stroke are the most frequent causes of death or disability worldwide. Due to their ability to dissolve blood clots, the thrombolytics are frequently used for their treatment. Improving the effectiveness of thrombolytics for clinical uses is of great interest. The knowledge of the multiple roles of the endogenous thrombolytics and the fibrinolytic system grows continuously. The effects of thrombolytics on the alteration of the nervous system and the regulation of the cell migration offer promising novel uses for treating neurodegenerative disorders or targeting cancer metastasis. However, secondary activities of thrombolytics may lead to life-threatening side-effects such as intracranial bleeding and neurotoxicity. Here we provide a structural biology perspective on various thrombolytic enzymes and their key properties: (i) effectiveness of clot lysis, (ii) affinity and specificity towards fibrin, (iii) biological half-life, (iv) mechanisms of activation/inhibition, and (v) risks of side effects. This information needs to be carefully considered while establishing protein engineering strategies aiming at the development of novel thrombolytics. Current trends and perspectives are discussed, including the screening for novel enzymes and small molecules, the enhancement of fibrin specificity by protein engineering, the suppression of interactions with native receptors, liposomal encapsulation and targeted release, the application of adjuvants, and the development of improved production systems.
ER  -

MIČAN, Jan, Martin TOUL, David BEDNÁŘ a Jiří DAMBORSKÝ. Structural Biology and Protein Engineering of Thrombolytics. \textit{Computational and Structural Biology Journal}. Amsterdam: Elsevier, 2019, roč.~17, č.~2019, s.~917-938. ISSN~2001-0370. Dostupné z: https://dx.doi.org/10.1016/j.csbj.2019.06.023.

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