• Title/Summary/Keyword: Molecular linkers

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Role of polyethylene glycol (PEG) linkers: trends in antibody conjugation and their pharmacokinetics

  • Kondapa Naidu Bobba;Abhinav Bhise;Subramani Rajkumar;Woonghee Lee;Jeongsoo Yoo
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.6 no.2
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    • pp.155-164
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    • 2020
  • Polyethylene glycol (PEG) has been the most commonly used polymer for the past few decades in the field of biomedical applications due to its gold standard stealth effect. PEGylation of antibody-drug conjugates, liposomes, peptides, nanoparticles, and proteins is done to improve their pharmaceutical efficacy and pharmacokinetic properties. PEGylation of antibodies with various PEG linkers improves targeting ability by increasing the blood circulation time and thus enhances the biodistribution profiles. It also assists in minimizing the immediate capture by the reticuloendothelial system. In this review, we summarize the effect of PEG linkers in an antibody conjugation and their pharmacokinetics in the field of biomedical imaging.

Rational Design of Coordination Polymers with Flexible Oxyethylene Side Chains

  • Choi, Eun-Young;Gao, Chun-Ji;Lee, Suck-Hyun;Kwon, O-Pil
    • Bulletin of the Korean Chemical Society
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    • v.33 no.4
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    • pp.1264-1267
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    • 2012
  • We rationally designed and synthesized metallopolymers with organic 1,4-benzenedicarboxylic acid (BDC) linkers with different lengths of oxyethylene side chains in order to examine the influence of side chains on the coordination characteristics. While in a previous report the BDC linkers with alkyl side chains were found to form three-dimensional (3D) isoreticular metal-organic framework (IRMOF) structures or one-dimensional (1D) coordination polymeric structures with short $-O(CH_2)_6CH_3$ or long $-O(CH_2)_9CH_3$ side chains, respectively, new BDC linkers with oxyethylene side chains of the same lengths, $-(OCH_2CH_2)_2CH_3$ and $-(OCH_2CH_2)_3CH_3$, form only 3D IRMOF structures. This result is attributed to the higher flexibility and smaller volume of oxyethylene side chains compared to alkyl side chains.

Recent progress of enzyme cleavable linker in antibody-drug conjugates: sulfatase and phosphatase

  • Sushil K. Dwivedi;Abhinav Bhise;Rajkumar Subramani;Jeongsoo Yoo
    • 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.

Molecular Networks via Coordination Polymerization. Synthesis and Characterization of 2-D Polymeric Cobalt(II) Compounds Containing 3,3'-Dipyridyl Ether Series

  • Jeong, Ok Sang;Kim, Yun Ju;Lee, Yeong A;Lee, Jae Gyeong;Yu, Gyeong Ho
    • Bulletin of the Korean Chemical Society
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    • v.21 no.1
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    • pp.39-43
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    • 2000
  • New coordination polymers of general form, $$[CoL_2X_2]_n$$ (L = 3,3'-oxybis(pyridine) (obp), 1,4-bis(3-pyri-doxy) benzene (bpob); X = Cl, NCS), have been prepared via a slow diffusion method. The reaction of the present linkers with cobalt(II) ion affords infinite 2-dimensional sheet products. For $[Co(obp) $_2Cl_2]_n$$, the local geometry of the cobalt center is an octahedral arrangement with four nitrogen donors and two chlorine ions in trans positions. $$[Co(bpob)_2(NCS)_2]_n$$ has provided a similar structure: the local geometry of the cobalt atom is an octahedral arrangement with four pyridine units and two NCS groups in transpositions. The obp and bpob linkers connect two cobalt(II) ions defining the edges of 40- and 60-membered $[Co(II)]_4$ ring, respectively. Thermal analyses of the coordination polymers show significant thermal behavior associated with the characteristic structures.

Oxygen-Silver Junction Formation for Single Molecule Conductance

  • Jo, Han Yeol;Yoo, Pil Sun;Kim, Taekyeong
    • Journal of the Korean Chemical Society
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    • v.59 no.1
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    • pp.18-21
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    • 2015
  • We use a scanning tunneling microscope based break-junction technique to measure the conductance of a 4,4'-dimethoxybiphenyl molecular junction formed with Ag and Au electrodes. We observe the formation of a clear molecular junction with Ag electrodes that result from stable Ag-oxygen bonding structures. However we have no molecular bonding formation when using Au electrodes, resulting in a tunneling current between the top and bottom metal electrodes. We also see a clear peak in the conductance histogram of the Ag-oxygen molecular junctions, but no significant molecular features are seen with Au electrodes. Our work should open a new path to the conductance measurements of single-molecule junctions with oxygen linkers.

Molecular Modeling Studies on the Functionalized MOF-5 (MOF-5 계열 화합물의 수소 흡착 용량 예측에 관한 분자모델링 연구)

  • Kim Dae Jin;Lee Tae Beom;Choi Seung Hun;Lee Eun Seong;Oh Yu Jin;Yun Ji Hye;Kim Ja Heon
    • 한국전기화학회:학술대회논문집
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    • 2004.06a
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    • pp.287-292
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    • 2004
  • In order to understand the relationship between molecular structure of Metal-Organic Framework(MOF) and capacity of hydrogen absorption, quantum mechanical calculations and grand canonical Monte Carlo simulations have been carried out on a series of MOF-5 having various organic linkers. The calculation results about specific surface area and electron density for various frameworks indicated that the capacity of the hydrogen storage is largely dependent on effective surface area rather than the free volume. Based on the iso-electrostatic potential surface from density functional calculation and the amount of adsorbed hydrogens from grand canonical Monte Carlo calculation, it was also found that the electron localization ground organic linker plays an important role in hydrogen capacity of MOFs.

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Effect of Linker for Immobilization of Glutathione on BSA-Assembled Controlled Pore Glass Beads

  • Chen, Li-Hua;Choi, Young-Seo;Park, Jung-Won;Kwon, Joseph;Wang, Rong-Shun;Lee, Tae-Hoon;Ryu, Sung-Ho;Park, Joon-Won
    • 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.

Analysis of quaternary structure of leucine-responsive regulatory protein (Lrp) by crosslink experiments (교차결합 실험을 통한 루신 대응 조절 단백질의 4차 구조 분석)

  • Lee, Euiho;Pokoo, Robert;Nguyen, Loi Thuan;Lee, Chan Yong
    • Korean Journal of Microbiology
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    • v.53 no.4
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    • pp.297-303
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    • 2017
  • Leucine-responsive regulatory protein (LRP) is a regulatory protein of molecular weight 18.8 kDa and is widely known to regulate many metabolic and functional activities of operons in Escherichia coli. The gene for Lrp from Escherichia coli in pQE system of 6 ${\times}$ His-tagging was expressed and $^3H$-labeled protein, as well as the wild type Lrp, was purified. The crosslink experiments were performed to analyze the quaternary structure of Lrp at high of $5{\mu}M$ and at low concentrations below $0.3{\mu}M$ with cross linkers, such as glutaraldehyde, 1, 2, 3, 4-diepoxy-butane (DEB), and ethylene glycol bis (succinimidyl succinate) (EGS). In the experiments, we found that the Lrp protein can be formed higher conformation states of tetramer, hexamer, octamer, as well as dimeric state when incubated with the above cross linkers.

Linker Scanning Analysis of the BPV-1 Upstream Regulatory Region

  • Kim, Hee-Dai;Rho, Jae-Rang;Choe, Joon-Ho
    • BMB Reports
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    • v.28 no.4
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    • pp.368-373
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    • 1995
  • The upstream regulatory region (URR) of bovine papillomavirus type 1 (BPV) contains promoters and a conditional transcriptional enhancer that is trans-activated by the viral E2 protein. After deleting the 5' and 3' ends of BPV URR, BamHI linkers were inserted into several positions of BPV URR without causing an addition or a deletion of URR sequences. Most linker scanning mutations did not show any effects on the transcription of P7940 and P89 promoters in BPV URR. However, several mutants showed reduced transcriptional activities. Based on our results we found that the AP-2 and Sp1 binding sites were important for basal level transcription of BPV URR in the absence of the E2 protein and that the CTF/NF-1 site is dispensable for E2 transactivation of BPV URR transcription.

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