Unconventional nucleotide analogues. Part XIII. (2S,4S)-2-hydroxymethyl- and 2-carboxy-4-(purin-9-yl)pyrrolidines.
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Adenine↗
Biomedical subjects
F M Kaspersen
Publications and source records attributed to F M Kaspersen.
Specific recognition of antibody-oligonucleotide conjugates by radiolabeled antisense nucleotides: a novel approach for two-step radioimmunotherapy of cancer.
One of the major challenges in radioimmunotherapy is the specific delivery of radioisotopes to tumor cells while minimizing normal tissue radiation. In this respect, the application of two-step pretargeting schemes generally leads to more favorable tumor to normal tissue uptake ratios than direct administration of radioimmunoconjugates. In this study, we present the specific hybridization of complementary DNA fragments as a novel recognition mechanism in pretargeting. Briefly, our strategy involves first administration of antibody-DNA conjugate, followed by targeting with radiolabeled complementary DNA (antisense DNA). Complementary oligodeoxynucleotides (14-mers, Tm = 57 degrees C), in which part of the phosphodiesters has been replaced by methylphosphonates (to ensure stability against nucleases), were prepared on a DNA synthesizer. The oligonucleotides were further derivatized via a uridine moiety at their 5'-end in such a way that radiolabeling or conjugation with antibodies could be accomplished. Both a murine IgG (anti-hCG) and the human anti-tumor IgM 16.88 were conjugated with one to three oligonucleotides via the heterobifunctional cross-linker SMCC. Incubation of these immunoconjugates with the radiolabeled antisense DNA revealed specific hybridization with the antibody-linked oligonucleotides. Antigen binding studies performed with antigen-coated matrices showed that the immunoreactivity of the antibody-DNA conjugate is preserved. Moreover, it is demonstrated that the radiolabeled DNA is still capable of hybridizing selectively with the oligonucleotides of the immunoconjugate, when the latter is bound to its antigen.
Animals↗
Electrophoretic method for the quantitative determination of a benzyl-DTPA ligand in DTPA monoclonal antibody conjugates.
A simple electrophoretic IEF procedure was developed for the quantitation of bifunctional DTPA ligand molecules in DTPA-protein conjugates. From a calibration plot of pI versus substitution ratios of reference conjugates, the concentrations of DTPA conjugated to protein were determined. Molar ratios of DTPA to protein agreed satisfactorily with the ratios obtained by a spectrophotometric technique using a colored yttrium(III) complex of arsenazo III. The IEF method was successfully applied on preparations of benzyl-DTPA to mAbs MOPC-21, SC-20 (aCEA), and human serum albumin.
Antibodies, Monoclonal↗