DIGITALIS RESEARCH IN BERLIN-BUCH - RETROSPECTIVE AND PERSPECTIVE VIEWS

被引:31
作者
REPKE, KRH
MEGGES, R
WEILAND, J
SCHON, R
机构
[1] Max-Delbrück-Centrum Für Molekulare Medizin, Berlin, D-13125
关键词
DIGITALIS; DRUG DESIGN; MEDICINAL CHEMISTRY; PHARMACEUTICALS; STEROIDS;
D O I
10.1002/anie.199502821
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
“The following remarks consist partially of matter of fact, and partially of opinion. The former will be permanent; the latter must vary with the detection of error, or the improvement of knowledge. I hazard them with diffidence, and hope they will be examined with candour.” These declarations, which stem from the famous book “An Account of the Foxglove and some of its Medical Uses” by physician William Withering in 1785 in which he introduced preparations from digitalis leaves in the therapy of dropsy (cardiac failure), are cited here by the senior author because of his awareness of the difficulties in presenting a balanced report on his life‐long research project on the further development of digitalis. His decision to devote himself to digitalis research originated at the bedside, when as a physician he experienced the grim final stages of cardiac failure in which no real help for the patients is possible. Unfortunately, his research project did not fit into the research program decreed by the Ministry of Science of the German Democratic Republic, so that he was ordered to stop the digitalis project in favor of biomembrane studies. Fortunately, he got round the ban simply by labeling the digitalis‐like acting steroids as probes for the cell membrane‐located Na+/K+‐transporting ATPase which he had just recognized as the digitalis target (receptor) enzyme. These and other ventures by the authors are collated here for the first time. The aim of this review is to foster straightforward research for solving a major challenge: the development of steroidal drugs for the prevention and cure of cardiac failure. Copyright © 1995 by VCH Verlagsgesellschaft mbH, Germany
引用
收藏
页码:282 / 294
页数:13
相关论文
共 165 条
  • [1] AKERA T, 1981, HDB EXPT PHARM, V56, P287
  • [2] DESIGN OF ENZYME-INHIBITORS USING ITERATIVE PROTEIN CRYSTALLOGRAPHIC ANALYSIS
    APPELT, K
    BACQUET, RJ
    BARTLETT, CA
    BOOTH, CLJ
    FREER, ST
    FUHRY, MAM
    GEHRING, MR
    HERRMANN, SM
    HOWLAND, EF
    JANSON, CA
    JONES, TR
    KAN, CC
    KATHARDEKAR, V
    LEWIS, KK
    MARZONI, GP
    MATTHEWS, DA
    MOHR, C
    MOOMAW, EW
    MORSE, CA
    OATLEY, SJ
    OGDEN, RC
    REDDY, MR
    REICH, SH
    SCHOETTLIN, WS
    SMITH, WW
    VARNEY, MD
    VILLAFRANCA, JE
    WARD, RW
    WEBBER, S
    WEBBER, SE
    WELSH, KM
    WHITE, J
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (07) : 1925 - 1934
  • [3] ARIENS EJ, 1977, 5TH MED CHEM P INT S, P409
  • [4] AUSTEL V, 1978, ARZNEIMITTELENTWICKL, P113
  • [5] THE THERMODYNAMIC ESSENCE OF THE REVERSIBLE INACTIVATION OF NA+/K+-TRANSPORTING ATPASE BY VARIOUS DIGITALIS DERIVATIVES IS RELAXATION OF ENZYME CONFORMATIONAL ENERGY
    BEER, J
    KUNZE, R
    HERRMANN, I
    PORTIUS, HJ
    MIRSALICHOVA, NM
    ABUBAKIROV, NK
    REPKE, KRH
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1988, 937 (02) : 335 - 346
  • [6] BOHL M, 1992, MOL STRUCTURE BIOL A, P91
  • [7] BROWN L, 1984, ARZNEIMITTELFORSCH, V34-1, P572
  • [8] DIGITALIS STRUCTURE-ACTIVITY RELATIONSHIP ANALYSES - CONCLUSIONS FROM INDIRECT BINDING-STUDIES WITH CARDIAC (NA++K+)-ATPASE
    BROWN, L
    ERDMANN, E
    THOMAS, R
    [J]. BIOCHEMICAL PHARMACOLOGY, 1983, 32 (18) : 2767 - 2774
  • [9] BROWN L, 1983, ARZNEIMITTEL-FORSCH, V33-1, P814
  • [10] CAPASSO JM, 1992, J BIOL CHEM, V267, P1150