Chan Hyuk Kim

Bispecific antibodies were constructed using genetically encoded unnatural amino acids with orthogonal chemical reactivity. A two-step process afforded homogeneous products in excellent yield. Using this approach, we synthesized an anti-HER2/anti-CD3 bispecific antibody, which efficiently cross-linked HER2+ cells and CD3+ cells. In vitro effector-cell mediated cytotoxicity was observed at picomolar concentrations.

A novel post-translationally modified amino acid, crotonyllysine (Kcr), was genetically incorporated into proteins in bacterial and mammalian cells using an evolved pyrrolysyl-tRNA/synthetase-tRNA pair. The ability to produce histones with homogenous, site-specific Kcr modifications will be valuable in elucidating the biological role of this recently identified post-translational modification.

Chimeric antigen receptor T (CAR-T) cells have demonstrated promising results against hematological malignancies, but have encountered significant challenges in translation to solid tumors. To overcome these hurdles, we have developed a switchable CAR-T cell platform in which the activity of the engineered cell is controlled by dosage of an antibody-based switch. Herein, we apply this approach to Her2-expressing breast cancers by engineering switch molecules through site-specific incorporation o

Short and to the point: A formal synthesis of platensimycin has been accomplished by employing a carbonyl ylide [3+2] cycloaddition reaction (see scheme). This short and facile enantioselective synthesis of the pivotal tetracyclic precursor requires 11 steps and proceeds in 20 % overall yield from isopropyl cyanoacetate. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z800568_s.pdf or from the author. Please note: The publisher

Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnat

Acute myeloid leukemia (AML), which is the most common acute adult leukemia and the second most common pediatric leukemia, still has a poor prognosis. Human C-type lectin-like molecule-1 (CLL1) is a recently identified myeloid lineage restricted cell surface marker, which is overexpressed in over 90% of AML patient myeloid blasts and in leukemic stem cells. Here, we describe the synthesis of a novel bispecific antibody, αCLL1-αCD3, using the genetically encoded unnatural amino acid, p-acetylphen

Four different formats of bispecific antibodies (bsAbs) were generated that consist of anti-Her2 IgG or Fab site-specifically conjugated to anti-CD3 Fab using the genetically encoded noncanonical amino acid. These bsAbs varied in valency or in the presence or absence of an Fc domain. Different valencies did not significantly affect antitumor efficacy, whereas the presence of an Fc domain enhanced cytotoxic activity, but triggered antigen-independent T-cell activation. We show that the bsAbs can

Despite the development of next-generation antiandrogens, metastatic castration-resistant prostate cancer (mCRPC) remains incurable. Here, we describe a unique semisynthetic bispecific antibody that uses site-specific unnatural amino acid conjugation to combine the potency of a T cell-recruiting anti-CD3 antibody with the specificity of an imaging ligand (DUPA) for prostate-specific membrane antigen. This format enabled optimization of structure and function to produce a candidate (CCW702) with

Kurz und prägnant: Mithilfe einer Carbonyl-Ylid-[3+2]-Cycloaddition gelang die formale Synthese von Platensimycin (siehe Schema). Die kurze und einfache enantioselektive Synthese der entscheidenden tetracyclischen Vorstufe erfordert elf Stufen und liefert das Produkt ausgehend von Cyanoessigsäureisopropylester in 20 % Gesamtausbeute. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2008/z800568_s.pdf or from the author. Please note: T

The total synthesis of (-)-amphidinolide E was accomplished by following a synthetic scheme that incorporates the labile C2 stereocenter at a very late stage. The oxolane unit was prepared by beta-alkoxyacrylate radical cyclization. The enyne metathesis reaction was employed for the synthesis of the side chain. The Kocienski-Julia reaction was used for the union of the two major fragments, and the Kita macrolactonization protocol was used for macrolide synthesis.

Eine neue posttranslational modifizierte Aminosäure, Crotonyllysin (Kcr), wurde mithilfe eines evolvierten Pyrrolysyl-tRNA/Synthetase-tRNA-Paares gentechnisch in Proteine in Bakterien- und Säugerzellen eingebaut. Die Fähigkeit, Histone mit homogenen ortsspezifischen KCr-Modifikationen herzustellen, wird helfen, die biologische Rolle dieser kürzlich identifizierten posttranslationalen Modifikation aufzuklären.

Seine einzigartigen Strukturmerkmale machen das cytotoxische marine Makrolid (−)-Amphidinolid E zu einem reizvollen Syntheseziel. Die Totalsynthese gelang nun durch Kombination der radikalischen Cyclisierung eines β-Alkoxyacrylats zum Oxolanring mit einer Kocienski-Julia-Olefinierung zur Bildung der E-konjugierten Doppelbindung und einer Lactonisierung zum Schließen des makrocyclischen Rings.

The characteristics of the volatilization of semi-volatile inorganic ions sampled on a Teflon filter were investigated using a backup nylon filter and annular denuders. The volatilization ratio (VR) was defined as the fraction of the concentration at the backup filter and denuder to the sum of the concentrations collected at the Teflon filter, backup filter, and denuder. Particles whose aerodynamic diameters are less than or equal to 2.5 µm (PM2.5) were sampled for 24 h each season from summer 2