Anti-idiotypic antibodies elicited by pterin recognize active site epitopes in dihydrofolate reductases and dihydropteridine reductase.

Archives of Biochemistry and Biophysics
S RatnamJ H Freisheim

Abstract

Monoclonal antibodies (mAbs) against antipterin immunoglobulin and dihydropteridine reductase (DHPR) and also polyclonal antibodies against human dihydrofolate reductase (DHFR) were obtained. The anti-idiotypic mAbs and anti-DHPR mAbs bind specifically to human DHFR, Escherichia coli DHFR, soybean seedling DHFR, and human DHPR in solid-phase immunoassays. Further, the mAbs bind to the native but not to the denatured forms of DHFRs. The monoclonal antibodies also inhibit the enzymatic activity of human DHFR but not that of human DHPR. Competitive solid-phase immunoassays show stoichiometric inhibition by methotrexate and partial inhibition by NADPH of mAb binding to human DHFR. Cyanogen bromide fragments derived from human DHFR (residues 15-52 and 53-111), containing several active site residues, bind partially to some of the monoclonal antibodies. Accordingly, polyclonal antibodies to peptide 53-111 of human DHFR cross-react to some extent with human DHPR. Data from competitive immunoassays in which the binding of the various mAbs was tested singly and in combination with other mAbs suggest that these antibodies bind to a common region on human DHFR. The results also indicate that the mAbs display some heterogeneity with respec...Continue Reading

References

Apr 17, 1978·European Journal of Biochemistry·R G Cotton, I G Jennings
Jul 1, 1978·Analytical Biochemistry·R HaymanM B Van der Weyden
May 17, 1988·Biochemistry·N J PrendergastJ H Freisheim
Jun 1, 1987·Archives of Biochemistry and Biophysics·S RatnamJ H Freisheim
Sep 1, 1973·Canadian Journal of Biochemistry·S CheemaK G Scrimgeour
Jul 1, 1981·The Biochemical Journal·F A FirgairaD M Danks

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Citations

Jul 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·I G JenningsR G Cotton
Feb 27, 2016·Human Mutation·Nenad Blau
Jan 6, 2004·Medicinal Research Reviews·Alberto PonzoneLuisa de Sanctis
Nov 7, 1996·Chemical Reviews·T. Joseph Kappock, John P. Caradonna

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