title: PEGylation and HAylation via catechol: α-Amine-specific reaction at N-terminus of peptides and proteins.
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 α-amines, avoiding the ε-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.
  
  
  
  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.
authors.affiliation: Department of Chemistry, KAIST, BK21 Plus Program, 291 University Rd., Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: In Taek
authors.initials: IT
authors.lastname: Song
authors.affiliation: Department of Chemistry, KAIST, BK21 Plus Program, 291 University Rd., Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Mihyun
authors.initials: M
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Ewha Womans University, 11-1 Daehyun-Dong, Seoul 120-750, Republic of Korea.
authors.forename: Hyukjin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences & Biomedical Research Center, 291 University Rd., Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Jinah
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, Republic of Korea.
authors.forename: Jae-Hyung
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Innotherapy Inc., ACE Hitech City 2, 25, Seonyu-ro 13-gil, Yeongdeungpo-gu, Seoul, Republic of Korea.
authors.forename: Moon Sue
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences & Biomedical Research Center, 291 University Rd., Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
authors.affiliation: Department of Chemistry, KAIST, BK21 Plus Program, 291 University Rd., Yuseong-gu, Daejeon 305-701, Republic of Korea. Electronic address: haeshin@kaist.ac.kr.
authors.forename: Haeshin
authors.initials: H
authors.lastname: Lee
mesh_terms: D000588:Amines / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D002396:Catechols / Q000737:chemistry*; D004921:Erythropoietin / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D007328:Insulin / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
chemical_list: D000588:Amines; D002396:Catechols; D007328:Insulin; D010455:Peptides; D011506:Proteins; D004921:Erythropoietin; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid; C028210:monomethoxypolyethylene glycol; C034221:catechol
keywords: Catechol; Chemoselective conjugation; HAylation; PEGylation; α-Amine