A one-pot multistep approach to α-azido-phosphonate and phosphonothioate diesters: Key intermediates in the synthesis of haptens for the generation of antibody ligases

Bioorganic and Medicinal Chemistry Letters

Volumn 10, Issue 9, 2000, Pages 915-918

  Harwig, Curtis W ^a   Hoffman, Timothy Z ^a   Wentworth, Anita D ^a   Janda, Kim D ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA AZIDO PHOSPHONATE ESTER; ESTER DERIVATIVE; HAPTEN; MONOCLONAL ANTIBODY; PHOSPHONOTHIOATE ESTER; UNCLASSIFIED DRUG;

ARTICLE; CATALYSIS; CHEMICAL MODIFICATION; DIASTEREOISOMER; DRUG SYNTHESIS; ESTERIFICATION; MOLECULAR RECOGNITION; PROTEIN DEGRADATION; REACTION ANALYSIS;

ANTIBODIES, MONOCLONAL; ANTIBODY SPECIFICITY; AZIDES; ESTERS; HAPTENS; LIGASES;

EID: 0034194353     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(00)00137-2     Document Type: Article

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32. In a typical screening assay, the disulfide 16 was mixed in equimolar amounts with TCEP in water for 5 min. To initiate the assay, this mixture was added to the aqueous buffer system [100 mM Bicine (pH 8.0), containing the esters or thioesters 1a-d (500 μM) and 2.5% DMSO in the presence or absence of antibody (20 μM)] to give an initial thiol 2 concentration of 1 mM. The rates of reaction were measured by monitoring the rate of formation of 4a-b (or 5) by HPLC (adsorbosphere-HS column, acetonitrile:water (0.1% TFA) mobile phase, detection at 230 nm). The antibody-mediated rates (for < 5% of reaction, during which the progress curves were linear) were directly compared with the observed rate for the non-catalyzed reaction under identical assay conditions.