http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Kim, Kristine M.,Yi, Eugene C.,Kim, Youngsoo Elsevier 2012 Methods Vol.56 No.2
<P><B>Abstract</B></P><P>Protein receptor–ligand interactions play important roles in mediating enzyme catalysis, signal transduction, and other protein functions. Immunoaffinity purification followed by mass spectrometry analysis is a common method for identifying protein receptor–ligand complexes. However, it is difficult to distinguish between specific protein binding partners and non-specifically bound proteins that co-purify with the complex. In addition, weakly interacting binding partners may dissociate from the protein receptor–ligand complexes during immunoaffinity purification. The combination of chemical crosslinking, affinity purification, and differential mass spectrometry analysis provides a direct method for capturing stable, weak, and transient protein interactions that occur <I>in vivo</I> and <I>in vitro</I>. This approach enables the identification of functional receptor–ligand binding partners with high confidence. Herein, we describe a differential mass spectrometry approach coupled with <I>in situ</I> chemical crosslinking and immunoaffinity purification for identifying receptor–ligand binding partners. In particular, we identified a functional, counter-ligand structure of the natural killer cell p30-related protein.</P>
Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics
Kim, Eunhee G.,Kim, Kristine M. The Korean Society of Applied Pharmacology 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.6
Antibody-drug conjugates utilize the antibody as a delivery vehicle for highly potent cytotoxic molecules with specificity for tumor-associated antigens for cancer therapy. Critical parameters that govern successful antibody-drug conjugate development for clinical use include the selection of the tumor target antigen, the antibody against the target, the cytotoxic molecule, the linker bridging the cytotoxic molecule and the antibody, and the conjugation chemistry used for the attachment of the cytotoxic molecule to the antibody. Advancements in these core antibody-drug conjugate technology are reflected by recent approval of Adectris$^{(R)}$(anti-CD30-drug conjugate) and Kadcyla$^{(R)}$(anti-HER2 drug conjugate). The potential approval of an anti-CD22 conjugate and promising new clinical data for anti-CD19 and anti-CD33 conjugates are additional advancements. Enrichment of antibody-drug conjugates with newly developed potent cytotoxic molecules and linkers are also in the pipeline for various tumor targets. However, the complexity of antibody-drug conjugate components, conjugation methods, and off-target toxicities still pose challenges for the strategic design of antibody-drug conjugates to achieve their fullest therapeutic potential. This review will discuss the emergence of clinical antibody-drug conjugates, current trends in optimization strategies, and recent study results for antibody-drug conjugates that have incorporated the latest optimization strategies. Future challenges and perspectives toward making antibody-drug conjugates more amendable for broader disease indications are also discussed.
Applications of cell-based phage display panning to proteomic analysis
Kristine M. Kim,MinJeong Kang,이유진 한국유전학회 2011 Genes & Genomics Vol.33 No.1
In the post-genomic era, proteomics together with genomic tools have led to powerful new strategies in basic and clinical research. These combined “omics” technologies are being integrated into the drug target discovery process. Unlike the genome,the proteome is a highly dynamic entity that requires techniques capable of analyzing on selected populations of proteins in specific biological conditions that reflect the proteins’functional characteristics. Antibodies have become one of the most important reagents for the analysis of selected populations of proteins, and the application of phage-display antibody libraries to high-throughput antibody generation against large numbers of various antigens provides a tool for proteome-wide protein expression analysis. In this review, we will discuss the utility of phage-display antibodies in proteomics applications, specifically for the discovery of novel disease markers and therapeutic targets.
Kim, Eunhee G.,Kwak, Soo Heon,Hwang, Daehee,Yi, Eugene C.,Park, Kyong Soo,Koo, Bo Kyung,Kim, Kristine M. Korean Diabetes Association 2016 Diabetes and Metabolism Journal Vol.40 No.2
<P><B>Background</B></P><P>The prevalence of novel type 1 diabetes mellitus (T1DM) antibodies targeting eukaryote translation elongation factor 1 alpha 1 autoantibody (EEF1A1-AAb) and ubiquitin-conjugating enzyme 2L3 autoantibody (UBE2L3-AAb) has been shown to be negatively correlated with age in T1DM subjects. Therefore, we aimed to investigate whether age affects the levels of these two antibodies in nondiabetic subjects.</P><P><B>Methods</B></P><P>EEF1A1-AAb and UBE2L3-AAb levels in nondiabetic control subjects (<I>n</I>=150) and T1DM subjects (<I>n</I>=101) in various ranges of age (18 to 69 years) were measured using an enzyme-linked immunosorbent assay. The cutoff point for the presence of each autoantibody was determined based on control subjects using the formula: [mean absorbance+3×standard deviation].</P><P><B>Results</B></P><P>In nondiabetic subjects, there were no significant correlations between age and EEF1A1-AAb and UBE2L3-AAb levels. However, there was wide variation in EEF1A1-AAb and UBE2L3-AAb levels among control subjects <40 years old; the prevalence of both EEF1A1-AAb and UBE2L3-AAb in these subjects was 4.4%. When using cutoff points determined from the control subjects <40 years old, the prevalence of both autoantibodies in T1DM subjects was decreased (EEFA1-AAb, 15.8% to 8.9%; UBE2L3-AAb, 10.9% to 7.9%) when compared to the prevalence using the cutoff derived from the totals for control subjects.</P><P><B>Conclusion</B></P><P>There was no association between age and EEF1A1-AAb or UBE2L3-AAb levels in nondiabetic subjects. However, the wide variation in EEF1A1-AAb and UBE2L3-AAb levels apparent among the control subjects <40 years old should be taken into consideration when determining the cutoff reference range for the diagnosis of T1DM.</P>
( Eunhee G Kim ),( Kristine M Kim ) 한국응용약물학회 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.6
Antibody-drug conjugates utilize the antibody as a delivery vehicle for highly potent cytotoxic molecules with specificity for tumor-associated antigens for cancer therapy. Critical parameters that govern successful antibody-drug conjugate development for clinical use include the selection of the tumor target antigen, the antibody against the target, the cytotoxic molecule, the linker bridging the cytotoxic molecule and the antibody, and the conjugation chemistry used for the attachment of the cytotoxic molecule to the antibody. Advancements in these core antibody-drug conjugate technology are reflected by recent approval of Adectris® (anti-CD30-drug conjugate) and Kadcyla® (anti-HER2 drug conjugate). The potential approval of an anti-CD22 conjugate and promising new clinical data for anti-CD19 and anti-CD33 conjugates are additional advancements. Enrichment of antibody-drug conjugates with newly developed potent cytotoxic molecules and linkers are also in the pipeline for various tumor targets. However, the complexity of antibody-drug conjugate components, conjugation methods, and off-target toxicities still pose challenges for the strategic design of antibody-drug conjugates to achieve their fullest therapeutic potential. This review will discuss the emergence of clinical antibody-drug conjugates, current trends in optimization strategies, and recent study results for antibody-drug conjugates that have incorporated the latest optimization strategies. Future challenges and perspectives toward making antibody-drug conjugates more amendable for broader disease indications are also discussed.