Identification, characterization, and engineering of glycosylation in thrombolytics

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F23%3A00079750" target="_blank" >RIV/00159816:_____/23:00079750 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14310/23:00131494

Result on the web

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0734975023000812?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0734975023000812?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.biotechadv.2023.108174" target="_blank" >10.1016/j.biotechadv.2023.108174</a>

Result language

angličtina

Original language name

Identification, characterization, and engineering of glycosylation in thrombolytics

Original language description

Cardiovascular diseases, such as myocardial infarction, ischemic stroke, and pulmonary embolism, are the most common causes of disability and death worldwide. Blood clot hydrolysis by thrombolytic enzymes and throm-bectomy are key clinical interventions. The most widely used thrombolytic enzyme is alteplase, which has been used in clinical practice since 1986. Another clinically used thrombolytic protein is tenecteplase, which has modified epitopes and engineered glycosylation sites, suggesting that carbohydrate modification in thrombolytic enzymes is a viable strategy for their improvement. This comprehensive review summarizes current knowledge on computational and experimental identification of glycosylation sites and glycan identity, together with methods used for their reengineering. Practical examples from previous studies focus on modification of gly-cosylations in thrombolytics, e.g., alteplase, tenecteplase, reteplase, urokinase, saruplase, and desmoteplase. Collected clinical data on these glycoproteins demonstrate the great potential of this engineering strategy. Outstanding combinatorics originating from multiple glycosylation sites and the vast variety of covalently attached glycan species can be addressed by directed evolution or rational design. Directed evolution pipelines would benefit from more efficient cell-free expression and high-throughput screening assays, while rational design must employ structure prediction by machine learning and in silico characterization by supercomputing. Perspectives on challenges and opportunities for improvement of thrombolytic enzymes by engineering and evolution of protein glycosylation are provided.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

20902 - Bioprocessing technologies (industrial processes relying on biological agents to drive the process) biocatalysis, fermentation

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Biotechnology Advances

ISSN

0734-9750

e-ISSN

1873-1899

Volume of the periodical

66

Issue of the periodical within the volume

SEP 2023

Country of publishing house

GB - UNITED KINGDOM

Number of pages

23

Pages from-to

108174

UT code for WoS article

001009152300001

EID of the result in the Scopus database

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