• Bulletin of the Korean Chemical Society
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• v.30 no.5
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• pp.1043-1046
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• 2009

Human protein tyrosine kinase-6 (PTK6) is a member of the non-receptor protein tyrosine kinase family and it is found in two-thirds of all breast tumors. Very recently, we proposed that the SH3 domain of PTK6 interacts with the linker region (Linker) between the SH2 and kinase domains, proving that the interaction between SH3 domain and Linker plays an important role in auto-inhibition mechanism. Residues from 1 to 191 corresponding region of SH3-SH2-Linker (SH32L) of PTK6 was cloned into the pET32a expression vector with Tobbaco etch virus (TEV) protease enzyme site by sequence homology and 3D structural model. The purified PTK6-SH32L was determined as a monomer conformation in solution. The amide proton resonances in the $^{15}N-^{1}H$ 2D-HSQC spectrum suggest that PTK6-SH32L possesses disordered structural region of the flexible/unstructured linker region. In addition, the backbone amide proton chemical shifts of the SH3 domain in the PTK6-SH32L differ from that of the independent domain, indicating that intra-molecular interaction between SH3 and Linker in the PTK6-SH32L is present.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.1
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• pp.33-40
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• 2021

Recently, antibody-drug conjugates (ADCs) are used to deliver efficient cytotoxic payloads selectively in cancer cells. In the designing of an ADC, the antibody is connected to a toxic payload via a covalent linker, which helps to solubilizes the typical hydrophobic payload as well as stabilizes the linkage over circulation. The development of the linkers for the antibody drug conjugate is still in demand. Initially, the acid, disulfide, and cathepsin-sensitive ADCs attracted considerable attention for the delivery of a potent cytotoxic payload but suffer from instability in human and mouse plasma with a short half-life. In addition, It also suffer from a solubility issue that induces aggregation, which is the major problem in their development. ADCs associated with sulfatase and phosphatase cleavable linker are highly soluble due to the anionic nature of sulfate and phosphate groups. The ADCs also showed high stability in human and mouse plasma. Therefore, to overcome these limitations, sulfatase and phosphatase cleavable linkers were developed. This review focuses on the recently reported advantages of sulfatase and phosphatase cleavable linkers for ADCs.

• Bulletin of the Korean Chemical Society
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• v.34 no.4
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• pp.1025-1029
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• 2013

In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between ${\alpha}$-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The $IC_{50}$ values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE ($IC_{50}=0.44{\pm}0.24{\mu}M$). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is $4.3{\pm}0.09{\mu}M$.

• Korean Chemical Engineering Research
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• v.46 no.6
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• pp.1081-1086
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• 2008

QDs-LEDs(quantum dot light emitting device) should contain well-organized arrays of QDs on an electron transport layer. Thin films of CdSe/ZnS core-shell QDs were successfully fabricated on $TiO_2$ substrates by using PDMS stamp and micro contact printing method. 2-Carboxyethylphosphonic acid(CAPO) and 1,6-hexanedithiol(HDT) were employed as molecular linkers in assembling CdSe/ZnS core-shell QDs with high-density and uniform array. The CAPO increased the binding strength between the QDs and the substrates, and the HDT induced the strong inter-particle attractions of assembled QDs. The assembling properties of QDs thin films were characterized by SEM, AFM, optical microscope and photoluminescence spectroscope(PL).

• Archives of Plastic Surgery
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• v.51 no.1
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• pp.20-26
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• 2024

The etiology and pathophysiology of delayed inflammatory reactions caused by hyaluronic acid fillers have not yet been elucidated. Previous studies have suggested that the etiology can be attributed to the hyaluronic acid filler itself, patient's immunological status, infection, and injection technique. Hyaluronic acid fillers are composed of high-molecular weight hyaluronic acids that are chemically cross-linked using substances such as 1,4-butanediol diglycidyl ether (BDDE). The mechanism by which BDDE cross-links the two hyaluronic acid disaccharides is still unclear and it may exist as a fully reacted cross-linker, pendant cross-linker, deactivated cross-linker, and residual cross-linker. The hyaluronic acid filler also contains impurities such as silicone oil and aluminum during the manufacturing process. Impurities can induce a foreign body reaction when the hyaluronic acid filler is injected into the body. Aseptic hyaluronic acid filler injections should be performed while considering the possibility of biofilm formation or delayed inflammatory reaction. Delayed inflammatory reactions tend to occur when patients experience flu-like illnesses; thus, the patient's immunological status plays an important role in delayed inflammatory reactions. Large-bolus hyaluronic acid filler injections can induce foreign body reactions and carry a relatively high risk of granuloma formation.

• Bulletin of the Korean Chemical Society
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• v.25 no.9
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• pp.1366-1370
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• 2004

Controlled pore glass bead was modified with bovine serum albumin (BSA), and glutathione (GSH) was immobilized through three kinds of linkers on top of BSA. Bis(3-sulfo-N-hydroxysuccinimide suberate) sodium salt $(BS^3)$, N-hydroxysuccinimide 3-(2-pyridyldithio)propionate (SPDP), or N-hydroxysuccinimide 4-maleimidobutyrate (GMBS) was introduced into the BSA-bound matrix. Subsequently, GSH was immobilized by addition of thiol side chain into the maleimido moiety, replacing a disulfide group, or formation of an amide group upon releasing 3-sulfo-N-hydroxysuccimide group. It was observed that conjugation methodology played a critical role for activity of the immobilized GSH. SDS-PAGE chromatogram showed that the matrix of glutathione immobilized on BSA through GMBS manifested high selectivity towards glutathione-S-transferase (GST) in cell lysate.

• 한국생물공학회:학술대회논문집
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• 2005.04a
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• pp.47-47
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• 2005

There are many different surface technologies currently applied for preparation of protein chips. However, it requires innovative surface chemistry for capture proteins to be immobilized on chip surface keeping their conformation and activity intact and their orientation right, while they bind tightly and densely in a given array spot. Proteogen has developed 'ProteoChip BP' coated with novel proprietary linker molecules $(ProLinker^{TM})$ for efficient and robust immobilizations of capture proteins by improving surface properties of molecular captures. It was demonstrated that $ProLinker^{TM}$ gave the best surface performance in preparation of protein microarray chip base plates among others currently available on the market. In particular, the $ProLinker^{TM}-based$ surface chemistry has demonstrated to provide excellent performance in preparation of 'Antibody Chip' for analysis of biomarkers as well as proteome expression profiles. The linker molecule has also shown to be well applicable for development of biosensors and micro-beads as well as protein microarray and nano-array. ProteoChip BP can be used either for preparation of high-density array by using a microarrayer or for preparation of 'Well-on-a-Chip' with low density array, which is better applicable for quantitative analysis of biomarkers or protein-protein interactions. The biomarker assay can be performed either by direct or sandwich methods of fluorescence immunoassay. Application of ProteoChip BP has been well demonstrated by the extensive studies of 1) tumor-marker assays, 2) new drug screening by using 'Integrin Chip' and 3) protein expression profile analysis. Some of experimental results will be presented.

• Journal of the Korean Magnetic Resonance Society
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• v.15 no.2
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• pp.137-145
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• 2011

Hsp33, a prokaryotic molecular chaperone, exerts holdase activity in response to oxidative stress. In this study, the stepwise conformational change of Hsp33 upon oxidation was monitored by NMR. In order to overcome its high molecular weight (33 kDa as a monomer and 66 kDa as a dimer), spectra were simplified using a selectively [$^{15}N$]His-labeled protein. All of the eight histidines were observed in the TROSY spectrum of the reduced Hsp33. Among them, three peaks showed dramatic resonance shifts dependent on the stepwise oxidation, indicating a remarkable conformational change. The results suggest that unfolding of the linker domain is associated with dimerization, but not entire region of the linker domain is unfolded.

• BMB Reports
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• v.42 no.11
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• pp.764-768
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• 2009

The tandem ubiquitin-interacting motif (UIM) domain located at the N-terminus of Receptor Associated Protein 80 (RAP80) plays a crucial role in ionizing radiation (IR)-induced DNA damage response. RAP80 translocates to sites of IR-induced DNA damage through interaction of its UIM domain with ubiquitinated H2A and Lys63-linked polyubiquitin chains. The exact mechanism, however, through which RAP80 associates with Lys63-linked polyubiquitin chains is not clear. Here, we show by in vitro GST-pull down assays that modifying the linker region between the tandem ubiquitin binding domains of RAP80 changes the binding affinity for Lys63-linked polyubiquitin chains and affects translocation to sites of DNA breaks. Based on these findings, we suggest that the length of the linker region between the tandem ubiquitin binding domains of RAP80 may be a key factor in the binding of RAP80 with Lys63-linked polyubiquitin chains as well as in the translocation of RAP80 to DNA break sites.

• Bulletin of the Korean Chemical Society
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• v.35 no.2
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• pp.383-391
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• 2014

Biotin-S-S-Phosphine was designed and synthesized as a potential tool for a proteomic study of O-GlcNAcmodified proteins. This reagent features a disulfide linker between a triarylphosphine moiety, which allows selective conjugation to azide-containing proteins, and a biotin moiety that can allow easy isolation through its strong affinity toward avidin-coated solid beads. The disulfide linkage within this reagent can allow the easy release of the bound molecules of interest, which is difficult to achieve when a biotin:avidin pair is used alone, by reducing the disulfide bond of the reagent with DTT. Preliminary in vitro biological assays with azidelabeled and unlabeled cell lysates and a pure protein Nup62 showed that the Biotin-S-S-Phosphine reagent is highly reactive toward the free thiol groups of proteins. When a molecular tool with a disulfide linker is applied to the enrichment of the molecules of interest from other species, it is important to block the free-thiols of the sample using exhaustive alkylation prior to the Staudinger ligation reactions to restore the bioorthogonal nature of this reaction.