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PEGylation and HAylation via catechol: alpha-Amine-specific reaction at N-terminus of peptides and proteins

Title
PEGylation and HAylation via catechol: alpha-Amine-specific reaction at N-terminus of peptides and proteins
Authors
Song, In TaekLee, MihyunLee, HyukjinHan, JinahJang, Jae-HyungLee, Moon SueKoh, Gou YoungLee, Haeshin
Ewha Authors
이혁진
SCOPUS Author ID
이혁진scopus
Issue Date
2016
Journal Title
ACTA BIOMATERIALIA
ISSN
1742-7061JCR Link1878-7568JCR Link
Citation
vol. 43, pp. 50 - 60
Keywords
PEGylationHAylationCatecholChemoselective conjugationalpha-Amine
Publisher
ELSEVIER SCI LTD
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The development of chemoselective, site-specific chemistries for proteins/peptides is essential for biochemistry, pharmaceutical chemistry, and other fields. In this work, we found that catechol, which has been extensively utilized as an adhesive molecule for material-independent surface chemistry and as a crosslinker in hydrogel preparation, specifically reacts with N-terminal alpha-amines, avoiding the epsilon-amine group in lysine. A conjugate of methoxy-poly(ethylene glycol)-catechol called mPEG-cat chemoselectively reacts with N-terminal amine groups at neutral pH resulting in site-specific PEGylation. To demonstrate the versatility of this catechol chemoselective reaction, we used four proteins (lysozyme, basic-fibroblast growth factor (bFGF), granulocyte-colony stimulating factor (G-CSF), insulin, and erythropoietin (EPO)) as well as two peptides (hinge-3 and laminin-derived peptide (LDP)). All the tested macromolecules showed N-terminal site-specific modifications. Furthermore, we prepared another catechol grafted conjugate called hyaluronic acid-catechol (HA-cat) to demonstrate that this catechol-involved chemoselective chemistry is not specific for PEG conjugates. This new catechol chemoselective chemistry could be a new platform for the functionalization of proteins and peptides for a variety of purposes. Statement of Significance Considering the fact that biological activities of proteins or peptides depend largely on their 3-dimensional conformation, the orientation-controllable reaction is very important for preserving the intrinsic functionality of them. In addition to PEG, many other bio-polymers such as oligonucleotides, antibodies, and oligosaccharides have been conjugated with proteins or peptides for various biomedical applications. Although several chemoselective conjugation chemistries have been reported, conjugation efficiencies are different depending on types of proteins or polymers, and thus there've been strong needs for the development of alternative strategy of chemoselective conjugation that can be applied for a variety of therapeutic proteins towards high biological activities. We are certain this new catechol chemoselective chemistry could be a new platform for the functionalization of proteins and peptides for various purposes. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
DOI
10.1016/j.actbio.2016.07.018
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약학대학 > 약학과 > Journal papers
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