caa a22 4500 477083722 CHVBK 20180405111456.0 cr unu---uuuuu 170330e19960401xx s 000 0 eng 10.1007/BF01919535 doi (NATIONALLICENCE)springer-10.1007/BF01919535 The amphiphilic properties of novenamines determine their activity as inhibitors of HIV-1 RNase H [Elektronische Daten] [I. Althaus, K. Franks, K. Langley, F. Kézdy, T. Peterson, S. Buxer, D. Decker, L. Dolak, R. Ulrich, F. Reusser] Few inhibitors of the RNase H function associatesd with the HIV-1 reverse transcriptase have been discovered to date. We observed that three novenamines, U-34445, U-35122, and U-35401, are specific inhibitors of the HIV-1 RT RNase H function. All three compounds are strong amphiphiles and contain one ionizable group. Hence, a priori, in aqueous solutions the inhibitors might exist in at least four different physical states, namely protonated monomers, ionized monomers, protonated micelles and ionized micelles. The three inhibitors all yielded anomalous dose-response curves, indicating that the four molecular species have different inhibitory potentials. In order to identify the inhibitory species, the amphiphilic properties of these compounds were studied. It was established that in alkaline solutions, around pH 8, all compounds are ionized and form micelles at concentrations above their CMC. Both the protonated and the ionized forms of these molecules from stable insoluble monomolecular layers at the air/water interface. The anomalies of the dose-response curves can be resolved by taking into account the fact that, in solution, the relative proportion of these molecules in each physical state depends on the pH and on their analytical concentration. Thus interpreted the results indicate that RNase H is inhibited only by the ionized micellar form of these compounds and not by their monomeric form. Around their pKa (∼pH5) the three componds reproducibly form uniformly sized, self-emulsified colloidal particles that may be used as an efficient drug delivery system. Birkhäuser Verlag, 1996 HIV RNase H nationallicence inhibitors nationallicence novenamines nationallicence micelles nationallicence HIV-1, HIV-2 : human immunodeficiency virus type 1 or 2, respectively nationallicence HIV RT : revese transcriptase nationallicence RNase H : HIV-1 RT associated nuclease nationallicence CMC : critical micellar concentration nationallicence MLV : murine leukemia virus nationallicence Althaus I. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut Franks K. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut Langley K. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut Kézdy F. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut Peterson T. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut Buxer S. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut Decker D. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut Dolak L. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut Ulrich R. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut Reusser F. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut Experientia Birkhäuser-Verlag 52/4(1996-04-01), 329-335 0014-4754 52:4<329 1996 52 18 https://doi.org/10.1007/BF01919535 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01919535 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Althaus I. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut NATIONALLICENCE 700 1- Franks K. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut NATIONALLICENCE 700 1- Langley K. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut NATIONALLICENCE 700 1- Kézdy F. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut NATIONALLICENCE 700 1- Peterson T. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut NATIONALLICENCE 700 1- Buxer S. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut NATIONALLICENCE 700 1- Decker D. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut NATIONALLICENCE 700 1- Dolak L. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut NATIONALLICENCE 700 1- Ulrich R. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut NATIONALLICENCE 700 1- Reusser F. The Upjohn Company, OU 7295-226, 301 Henrietta Street, 49001, Kalamazoo, Michigan, USA aut NATIONALLICENCE 773 0- Experientia Birkhäuser-Verlag 52/4(1996-04-01), 329-335 0014-4754 52:4<329 1996 52 18 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer