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Peptide-Directed Photo-Cross-Linking for Site-Specific Conjugation of IgG
Park, Jisoo,Lee, Yumi,Ko, Byoung Joon,Yoo, Tae Hyeon American Chemical Society 2018 Bioconjugate chemistry Vol.29 No.10
<P>Conjugation of antibody has expanded its applications in therapeutics and diagnostics, and various methods have been developed based on chemical or enzymatic reactions. However, the majority of them have focused on synthetic molecules such as small molecules, nucleic acids, or synthetic materials, but site-specific conjugation of antibody with protein cargo has rarely been demonstrated. In this Communication, we report a PEptide-DIrected Photo-cross-linking (PEDIP) reaction for site-specific conjugation of IgG with protein using an Fc-binding peptide and a photoreactive amino acid analogue, and demonstrate this method by developing an immunotoxin composed of a Her2-targeting IgG (trastuzumab) and an engineered <I>Pseudomonas</I> exotoxin A (PE24). The ADP-ribosylation of eukaryotic elongation factor-2 by the bacterial toxin inhibits the ribosomal translation of protein, and the trastuzumab-PE24 conjugate exhibited the cytotoxicity toward Her2-overexpressing cell lines. The PEDIP reaction can also be applied for many other types of cargo with slight modifications of the method.</P> [FIG OMISSION]</BR>
Clinical significance of anti-dense fine speckled 70 antibody in patients with fibromyalgia
( Jisoo Jeong ),( Dong Hyun Kim ),( Gun Park ),( Suyeon Park ),( Hyun-sook Kim ) 대한내과학회 2019 The Korean Journal of Internal Medicine Vol.34 No.2
Background/Aims: Fibromyalgia (FM) is a common rheumatologic disease characterized by chronic widespread pain, along with various clinical manifestations including atypical autoimmune characteristics. Despite its high prevalence, there remain no approved laboratory tests to identify specific manifestations of FM, or to rule out FM from other rheumatic diseases. Anti-dense fine speckled 70 (anti-DFS70) antibodies were initially identified as a form of anti-nuclear antibodies in a patient with interstitial cystitis. Anti-DFS70 antibodies are found in ≤ 10% of healthy individuals, but have suggestive negative association with autoimmune diseases; however, the clinical significance of these autoantibodies in FM patients remains poorly understood. Methods: We examined 39 patients with FM, along with 17 patients with systemic lupus erythematosus (SLE), and 19 healthy individuals (HI). Patients were compared based on physical measurements, disease duration, tender point counts, FM Impact Questionnaire (FIQ) scores, visual analog scale (VAS) for pain, somatic symptoms, and anti-DFS70 antibodies. Results: Levels of anti-DFS70 antibodies were significantly higher in the FM and HI groups than in those with SLE. Both anti-DFS70 antibodies and VAS scores were positively correlated with FM. Within the FM group, patients with arthralgia had higher anti-DFS70 antibody values compared to those without arthralgia (p = 0.024); antibody levels were also higher in patients with sleep disturbances relative to those without sleep issues (p = 0.024). In contrast, there were no correlations between anti-DFS70 antibodies and age, body mass index, disease duration, tender point counts, FIQ, short-form health survey results, or other clinical manifestations. Conclusions: Anti-DFS70 antibodies may represent a useful biomarker for differentiating between FM and other autoimmune diseases. The levels of anti-DFS70 antibodies were also significantly higher among patients with arthralgia and sleep disturbances. Further investigations are necessary to evaluate the relationships between anti-DFS70 antibodies and other cytokines as a predictive marker for pain.
Park, Jisoo,Choi, Woochan,Dar, Abdul Rouf,Butcher, Rebecca A.,Kim, Kyuhyung Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.1
Animals need to be able to alter their developmental and behavioral programs in response to changing environmental conditions. This developmental and behavioral plasticity is mainly mediated by changes in gene expression. The knowledge of the mechanisms by which environmental signals are transduced and integrated to modulate changes in sensory gene expression is limited. Exposure to ascaroside pheromone has been reported to alter the expression of a subset of putative G protein-coupled chemosensory receptor genes in the ASI chemosensory neurons of C. elegans (Kim et al., 2009; Nolan et al., 2002; Peckol et al., 1999). Here we show that ascaroside pheromone reversibly represses expression of the str-3 chemoreceptor gene in the ASI neurons. Repression of str-3 expression can be initiated only at the L1 stage, but expression is restored upon removal of ascarosides at any developmental stage. Pheromone receptors including SRBC-64/66 and SRG-36/37 are required for str-3 repression. Moreover, pheromone-mediated str-3 repression is mediated by FLP-18 neuropeptide signaling via the NPR-1 neuropeptide receptor. These results suggest that environmental signals regulate chemosensory gene expression together with internal neuropeptide signals which, in turn, modulate behavior.
Peptide-directed Photocrosslinking for Site-specific Conjugation of Native Antibody
Jisoo PARK,Tae Hyeon YOO 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10
Antibody-based conjugates have become an essential component in a variety of applications from immunoassays especially to drug conjugates because of their proven efficacy and selectivity to target cancer cell. Herein, we describe a peptide-directed photo-crosslinking reaction as a novel site-specific conjugation method of IgG using an Fc-binding peptide and a photoreactive amino acid analogue for generation homogeneous IgG-toxin conjugates.