Graham Holmwood
Bayer
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Graham Holmwood.
Bioorganic & Medicinal Chemistry | 2009
Graham Holmwood; Michael Schindler
We review the impact of protein X-ray crystallography on the rational design of insecticides that act as agonists of the ligand-binding domain of the Ecdysone receptor (EcR). As the EcR is a target specific to insects, these compounds potentially constitute new chemical classes of safe insecticides. The increased insight relative to that from ligand-only based (Quantitative) Structure-Activity Relations (QSARs), classical 2D-Hansch type or 3D-CoMFA/CoMSIA (Comparative Molecular Field/Similarity Analysis), is discussed. The importance of protein X-ray structure determination in support of the discovery process is stressed as the simplistic lock-and-key picture fails due to the remarkable flexibility of the EcR ligand binding site. Several new non-steroidal chemical classes of ecdysone agonists, designed by guidance from protein X-ray studies, are described.
Annals of the New York Academy of Sciences | 1988
Dieter Berg; Manfred Plempel; Karl-Heinz Buchel; Graham Holmwood; Klaus Stroech
Sterol biosynthesis inhibitors such as the imidazoles and 1,2,4-triazoles are generally regarded as inhibitors of sterol C-14 demethylation. Neither the MIC values nor the data for direct interaction with the cytochrome P-450 responsible for oxidative C-14 methyl removal, however, fully explain the observed in vivo efficacy. The first generation of azoles, which includes clotrimazole and miconazole, has been supplemented by a second generation, and azoles of the new generation are capable of additional effects on sterol biosynthesis. With the new azoles, for example, delta 5 sterols may accumulate, the accumulation being due to additional sites of inhibition in sterol biosynthesis or to direct membrane-azole interactions. Ketoconazole, itraconazole, and vibunazole are representative of the azoles of the second generation. Finally, a third generation of azoles has been discovered. Azoles of this generation, which include fluconazole, show almost negligible in vitro potency against saprophytically grown fungi but excellent in vivo efficacy. These compounds specifically affect parasitic forms of fungi, thus blocking invasion processes, and interfere directly with the plasma membrane, as shown in leakage experiments. Such secondary effects obviously enhance in vivo potency.
Archive | 1981
Graham Holmwood; Karl H. Buchel; Klaus Lurssen; Paul-Ernst Frohberger; Wilhelm Brandes
Archive | 1985
Graham Holmwood; Karl H. Buchel; Klaus Lurssen; Paul-Ernst Frohberger; Wilhelm Brandes
Archive | 1992
Georg-Wilhelm Dr Ludwig; Otto Exner; Wilfried Paulus; Karl-Heinz Buchel; Graham Holmwood
Archive | 1985
Graham Holmwood; Karl H. Buchel; Klaus Lurssen; Paul-Ernst Frohberger; Wilhelm Brandes
Archive | 1987
Graham Holmwood; Erik Regel; Gerhard Jager; Karl H. Buchel; Klaus Lurssen; Paul-Ernst Frohberger; Wilhelm Brandes; Volker Dr. Paul
Archive | 1980
Graham Holmwood; Paul-Ernst Frohberger; Wilhelm Brandes; Volker Dr. Paul
Archive | 1978
Graham Holmwood; Paul-Ernst Frohberger; Wilhelm Brandes; Volker Dr. Paul
Archive | 1982
Klaus Lurssen; Graham Holmwood; Wolfgang Kramer; Erik Ing. Grad. Regel; Wolf Reiser; Rolf Schroder