De Clercq Research Articles

118 Particular characteristics of the anti-herpesvirus activity of (1′S,2′ R)-9-[[1′,2′-bis(hydroxymethyl)cycloprop-1′-yl]methyl]guanine (A-5021) : J. Neyts and E. De Clercq Rega Institute for Medical Research, K.U.Leuven, B-3000 Leuven, Belgium

N-9 alkylated materials are the sole products obtained from extended reaction of 2-aminopurines (potential guanine precursors) with Michael acceptors. This was used as the basis for a highly regioselective synthesis of famciclovir, the oral form of the anti-herpesvirus agent penciclovir.

Selected chemotherapy and seasonally transmitted Schistosoma haematobium infections in the middle valley of the Senegal River Basin

Journal Article Selected chemotherapy and seasonally transmitted Schistosoma haematobium infections in the middle valley of the Senegal River Basin Get access D. De Clercq, D. De Clercq ∗ 1Department of Parasitology, University of Gent (RUG), Faculty of Veterinary Medicine, Salisburylaan 133, B-9820 Merelbeke, Belgium2Région Médicale de Saint Louis, B.P. 394, Saint Louis, Senegal ∗Author for correspondence. Search for other works by this author on: Oxford Academic PubMed Google Scholar C. Hanne, C. Hanne 2Région Médicale de Saint Louis, B.P. 394, Saint Louis, Senegal Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Vercruysse J. Vercruysse 1Department of Parasitology, University of Gent (RUG), Faculty of Veterinary Medicine, Salisburylaan 133, B-9820 Merelbeke, Belgium Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 94, Issue 2, March-April 2000, Pages 198–199, https://doi.org/10.1016/S0035-9203(00)90276-1 Published: 01 April 2000 Article history Received: 11 October 1999 Accepted: 09 November 1999 Published: 01 April 2000

Mammalian 5′(3′)-Deoxyribonucleotidase, cDNA Cloning, and Overexpression of the Enzyme in Escherichia coli and Mammalian Cells

5'(3')-Deoxyribonucleotidase is a ubiquitous enzyme in mammalian cells whose physiological function is not known. It was earlier purified to homogeneity from human placenta. We determined the amino acid sequences of several internal peptides and with their aid found an expressed sequence tag clone with the complete cDNA for a murine enzyme of 23.9 kDa. The DNA was cloned into appropriate plasmids and introduced into Escherichia coli and ecdyson-inducible 293 and V79 cells. The recombinant enzyme was purified to homogeneity from transformed E. coli and was found to be identical with the native enzyme. After induction with ponasterone, the transfected mammalian cells showed a gradual increase of enzyme activity. A human expressed sequence tag clone contained a large part of the cDNA of the human enzyme but lacked the 5'-end corresponding to 51 amino acids of the murine enzyme. Several polymerase chain reaction-based approaches to find this sequence met with no success. A mouse/human hybrid cDNA that had substituted the missing human 5'-end with the corresponding mouse sequence coded for a fully active enzyme.

Synthesis and anti-HIV activity of cosalane analogues incorporating nitrogen in the linker chain

Introduction of an amido group or an amino moiety into the alkenyl linker chain of cosalane (1) provided a new series of analogues 3–8. The new compounds were evaluated as inhibitors of the cytopathic effect of HIV-1 and HIV-2 in cell culture. The replacement of the 1′ and 2′ carbons in the linker chain of 1 by an amido group was generally tolerated. The length of the linker chain and the stereochemistry of the substituent at C-3 of the steroidal ring had significant effects on the antiviral activity and potency. Incorporation of an amino moiety into the linker completely abolished the anti-HIV activity. There are several steps in the HIV replication cycle that have been proposed as targets for the development of therapeutic agents (De Clercq, E. J. Med. Chem.1995, 38, 2491; De Clercq, E. Pure Appl. Chem.1998, 70, 567). However, currently approved anti-HIV drugs are only directed against the viral enzymes reverse transcriptase or protease (Carpenter, C. C. J.; Fischl, M. A.; Hammer, S. M.; Hirsch, M. S.; Jacobsen, D. M.; Katzenstein, D. A.; Montaner, J. S. G.; Richman, D. D.; Saag, M. S.; Schooley, R. T.; Thompson, M. A.; Vella, S.; Yeni, P. G.; Volberding, P. A. JAMA1998, 280, 78). Drugs capable of interfering with other steps of the virus life cycle will be highly valuable in the antiretroviral therapy of AIDS, as they will have different patterns of resistance mutations than the drugs currently used clinically. In addition, their utilization in combination with other therapeutic agents could provide more potent drug ‘cocktails’ capable of completely suppressing virus replication. Consequently, there is an urgent need for the discovery of clinically useful anti-HIV agents possessing novel mechanisms of action.

Analysis of the complications of the piggy-back technique in 1112 liver transplants: Surgical technique

22. Zutter MM, Martin PJ, Sale GE, et al. Epstein-Barr-virus asso-ciated B cell lymphoproliferative disorders after bone marrowtransplantation. Blood 1988; 72: 520.23. Renard TH, Andrews WS, Foster ME. Relationship betweenOKT3 administration, EBV conversion, and the lymphoprolif-erative syndrome in pediatric liver transplant recipients.Transplant Proc 1991; 23: 1473.24. Davis CL, Harrison KL, McVicar JP, Forg PJ, Bronner MP,Marsh CL. Antiviral prophylaxis and the Epstein Barr virus-related post-transplant lymphoproliferative disorder. ClinTransplant 1995; 9: 53.25. Yao QY, Ogan P, Rowe M, Rickinson AB. Epstein-Barr-virustreated B cells persist in the circulation of aciclovir-treatedvirus carriers. Int J Cancer 1989; 43: 61.26. Kuo PC, Dafoe DC, Alfrey EJ, Sibley RK, Scandling JD. Post-transplant lymphoproliferative disorders and Epstein-Barr vi-rus prophylaxis. Transplantation 1995; 59: 135.27. Darenkov IA, Marcarelli MA, Basadonna GP, et al. Reducedincidence of Epstein-Barr virus-associated posttransplant lym-phoproliferative disorder using preemptive antiviral therapy.Transplantation 1997; 64: 848.28. Neyts J, Andrei G, De Clercq E. The novel immunosuppressiveagent mycophenolate mofetil markedly potentiates the anti-herpesvirus activities of aciclovir, ganciclovir and penciclovirin vitro and in vivo. Antimicrob Agents Chemother 1998; 42:216.29. Tressler RJ, Garvin LJ, Slate DL. Anti-tumor activity of myco-phenolate mofetil against human and mouse tumors in vivo.Int J Cancer 1994; 57: 568.30. Fleiss JL. Statistical methods for rates and proportions, 2nd ed.New York: Wiley, 1981: 38.31. Alfrey EJ, Friedman AL, Grossman RA, et al. A recent decreasein the time to development of monomorphous and polymor-phous posttransplantlymphoproliferative disorder. Transplan-tation 1992; 54: 250.32. Ciancio G, Siquijor AP, Burke GW, et al. Post-transplant lym-phoproliferative disease in kidney transplant patients in thenew immunosuppressive era. Clin Transplant 1997; 11: 243.33. Morris RE. Transplantation. Beware: shifting paradigm ahead.Lancet 1996; 1 (suppl II): 26.Received 3 July 1998.Accepted 11 December 1998.

Synthetic influenza viral double-stranded RNA induces an acute-phase response in rabbits

Numerous studies have characterized the physiological effects of synthetic, high-molecular-weight, homopolymeric, double-stranded RNA (dsRNA), particularly polyriboinosinic.polyribocytidylic acid [Carter and De Clercq (1974): Science 186:1172-1178], but limited information exists regarding the physiological effects of dsRNA of viral composition and size. In this report, we determined sleep and fever responses of rabbits to intracerebroventricular injection of different doses of synthetic viral dsRNA (either 108 base pairs or 661 base pairs) derived from the N-terminal sequence of gene segment 3 of the A/PR/8/34-H1N1 (PR8) influenza virus. Both the108-mer and the 661-mer dsRNAs increased nonrapid eye movement sleep, suppressed rapid eye movement sleep, and induced fever. The 661-mer dsRNA had more potent somnogenic and pyrogenic effects than the 108-mer dsRNA on the basis of weight. Neither single-stranded RNA from the corresponding sequences had significant effects on sleep or brain temperature. These results demonstrate for the first time that low-molecular-weight, viral dsRNA has the stability in vivo that is required to induce the fever and sleep changes found in natural viral infections, and the hypothesis is supported that virus-associated dsRNA may be responsible for initiating the acute-phase response during viral infections.

The Leiden Cabinet of Physics: A Descriptive Catalogue

Reviewed by: The Leiden Cabinet of Physics: A Descriptive Catalogue * Deborah Jean Warner (bio) The Leiden Cabinet of Physics: A Descriptive Catalogue. By Peter de Clercq. Leiden: Museum Boerhaave, 1997. Pp. 198; illustrations, bibliography, index. Fl 95.00. This catalog describes some three hundred objects that once belonged to the Cabinet of Physics at the University of Leiden and are now housed in the Museum Boerhaave in that city. All were made between about 1660 and 1810; many were used by Leiden’s famous and influential physicists Willem Jacob ‘sGravesande and his successor, Petrus van Musschenbroek. Their elegant designs and finishes are indicative of their eighteenth-century origins, but the basic forms are still seen in science classes and science museums around the world. The bulk of the objects (including the air pumps and electrical machines) would generally be considered scientific instruments, but a surprising number represent technologies common in the Netherlands in the eighteenth century. These include a hoist, a capstan, a windlass, a winch, a pile driver, a corn and hulling mill, a sawmill, a drainage mill, a dredger, various pumps, and steam engines after Savery and Newcomen. The artifacts are organized into the categories of mechanics, fluids, pneumatics, optics, heat, magnetism and electricity, machine models, and “other apparatus.” As the first university to introduce courses in the new experimental natural philosophy, Leiden is understandably proud of its scientific heritage. In [End Page 136] keeping with this tradition, the Museum Boerhaave has filled its historic building with informative and accessible exhibits and has sponsored a series of catalogs that enable us to analyze and appreciate its objects from afar. The catalog at hand is intelligently organized and handsomely produced. For each object, there is a clear photograph and a succinct description, enriched with information about its date, dimensions, maker, and user(s), and references to publications concerning it and/or similar objects. Deborah Jean Warner Ms. Warner is curator of the physical sciences collection at the National Museum of American History and editor of Rittenhouse, a quarterly journal of the American instrument enterprise. Footnotes * Permission to reprint a review published here may be obtained only from the reviewer. Copyright © 1999 the Society for the History of Technology

Free and bound fatty acid oxidation products in archaeological ceramic vessels

While oxidation products of unsaturated fatty acids, for example dicarboxylic acids (hereafter diacids), must form during the use of unglazed ceramic vessels for the processing of animal and plant products, such components have never been observed during studies of absorbed lipids. Their absence from the extractable lipid fraction is presumed to be the result of their loss from potsherds through groundwater leaching. Lipid oxidation products including short-chain dicarboxylic acids, ω-hydroxy acids and longer-chain hydroxy and dihydroxy acids have now been observed as components probably covalently bound into solvent insoluble residues of potsherds recovered from waterlogged deposits. These components were only revealed following alkaline treatment of the insoluble residues. A similar mixture of diacids was observed in high abundance in the free lipid fraction of vessels recovered from an exceptionally arid deposit where groundwater leaching would never have occurred. These results confirm the formation of oxidation and probable polymerization products of unsaturated fatty acids during vessel use and burial.

At the Sign of the Oriental Lamp: The Musschenbroek Workshop in Leiden. 1660–1750 by Peter de Clercq

technology and culture Book Reviews 141 technology, urban historians, and anyone seeking an unusual glimpse of life in 17th-century Amsterdam. Daniel Winer Mr. Winer is a Ph.D. candidate in the Hagley Program at the University of Dela­ ware; his dissertation is on the development and meaning of firefighting from the 17th to 19th centuries. At the Sign ofthe Oriental Lamp: The Musschenbroek Workshop in Leiden. 1660-1750. By Peter de Clercq. Rotterdam: Erasmus, 1997. Pp. 326; illustrations, tables, appendixes, notes, bibliography, index. Hfl. 69.50 (paper). Recent years have seen a growing number of historians coming to appreciate the material aspects ofscience and beginning to examine both the apparatuses with which observations, experiments, and demonstrations were made—optical instruments such as telescopes and microscopes, and philosophical instruments such as whirling tables and air pumps and, later, electrostatic machines—and the in­ strument-makers and dealers whose technical sophistication and business acumen turned rough ideas into commercial products. Pe­ ter de Clercq, a curator in the Museum Boerhaave in Leiden, has made an important contribution to this literature with this intelli­ gent and lucid account of the Musschenbroek workshop, one of the first important centers of production of instruments designed for the new natural philosophy. The text presents a close examination of the scientific instrument business at a time when production still occurred in workshops and when distribution was still by direct sales from maker to customer. Appendices offer a preliminary checklist of extant Musschenbroek instruments and transcriptions of the eight extant Musschenbroeck trade catalogs, some of which are known through only one copy. The Musschenbroek family setded in Leiden in the early years of the 17th century, establishing a brass foundry at the Sign of the Ori­ ental Lamp. Their involvement with science began around 1660, when students and faculty at the nearby University of Leiden asked Samuel van Musschenbroek to supply them with microscopes and anatomical instruments. Johann van Musschenbroek, who took charge of the workshop following his brother’s death in 1681, ex­ panded the range of instruments and circle of customers. The busi­ ness expanded still further under the leadership of Johann’s son Jan, who ran the firm from 1707 until his death in 1748. Jan’s most important customer was Willem ’sGravesande, a professor at the Uni­ versity of Leiden, who purchased numerous instruments for his ex­ periments and classroom demonstrations, and who depicted many ofthem in his influential textbook, known in English as Mathematical 142 Book Reviews TECHNOLOGY AND CULTURE Elements ofNatural Philosophy, confirm’d by Experiments, or an Introduc­ tion to Sir Isaac Newton’s Philosophy. Other customers ranged from an anonymous burgemeesterto the stadholderWilliam IV and his educated wife, Anne of Hanover. Most of the Musschenbroek’s customers were in the Netherlands, but some were in Sweden, Germany, Italy, and Russia (but apparently none in France or Great Britain). The air pump was the most emblematic instrument of the new natural philosophy and, not surprisingly, the Musschenbroeks’ most important product. Although very few shop records survive, de Clercq has unearthed evidence of about forty Musschenbroek air pumps and estimates that this represents about one-third to onehalf of the firm’s total production. He also argues that by 1700 the Musschenbroeks were the leading purveyor of air pumps in Europe. This aspect of the story began in 1675 when Samuel made an air pump for Burchard de Voider, the first Leiden professor to teach natural philosophy. Voider had recently made a trip to England, seen the air pump that Robert Hooke had made for Robert Boyle, and desired a similar one for his own use. This instrument is now in the collections of the Museum Boerhaave. In 1679 Volder’s suc­ cessor, Wolferd Senguerd, asked Samuel to build an air pump of a somewhat different form; this design proved to be substantially eas­ ier to manipulate than the English model. It is clear that the Musschenbroeks had close collaborations with academics and that several Musschenbroek instruments incorpo­ rated important innovations, but there are few records indicating who invented what. De Clercq’s answer to the credit question, which I believe to be correct, is that scholars and craftsmen often possessed...

African Material Culture ed. by Mary Jo Arnoldi, et al

142 Book Reviews TECHNOLOGY AND CULTURE Elements ofNatural Philosophy, confirm’d by Experiments, or an Introduc­ tion to Sir Isaac Newton’s Philosophy. Other customers ranged from an anonymous burgemeesterto the stadholderWilliam IV and his educated wife, Anne of Hanover. Most of the Musschenbroek’s customers were in the Netherlands, but some were in Sweden, Germany, Italy, and Russia (but apparently none in France or Great Britain). The air pump was the most emblematic instrument of the new natural philosophy and, not surprisingly, the Musschenbroeks’ most important product. Although very few shop records survive, de Clercq has unearthed evidence of about forty Musschenbroek air pumps and estimates that this represents about one-third to onehalf of the firm’s total production. He also argues that by 1700 the Musschenbroeks were the leading purveyor of air pumps in Europe. This aspect of the story began in 1675 when Samuel made an air pump for Burchard de Voider, the first Leiden professor to teach natural philosophy. Voider had recently made a trip to England, seen the air pump that Robert Hooke had made for Robert Boyle, and desired a similar one for his own use. This instrument is now in the collections of the Museum Boerhaave. In 1679 Volder’s suc­ cessor, Wolferd Senguerd, asked Samuel to build an air pump of a somewhat different form; this design proved to be substantially eas­ ier to manipulate than the English model. It is clear that the Musschenbroeks had close collaborations with academics and that several Musschenbroek instruments incorpo­ rated important innovations, but there are few records indicating who invented what. De Clercq’s answer to the credit question, which I believe to be correct, is that scholars and craftsmen often possessed overlapping skills and an appreciation for one another. Deborah Warner Ms. Warner is curator of the physical sciences collections at the National Museum of American History and editor of Rittenhouse, a quarterlyjournal focusing on the history of the American scientific instrument enterprise. African Material Culture. Edited by Mary Jo Arnoldi, Christraud M. Geary, and Kris L. Hardin. Bloomington: Indiana University Press, 1996. Pp. xii+ 369; illustrations, maps, figures, tables, notes, index. $49.95 (cloth); $24.50 (paper). As the rubric “material culture” becomes increasingly fashion­ able, it also becomes more difficult to define. This collection of pa­ pers, originally presented at a conference in Bellagio, Italy, in 1988, exemplifies some of the contradictory problems posed in using such a category. While it may seem useful for bringing together scholars of different academic disciplines who study objects, there is always tin rloncror rx-f 1 ex ci r-| q* ---------------------- — ,1.-1 1 .1 TECHNOLOGY AND CULTURE Book Reviews 143 disciplines and then floating aimlessly, without a direction or desti­ nation in mind. In some respects this book indicates that the confer­ ence, which was intended specifically to address just these kinds of problems, did not entirely meet its objectives. The authors represent the disciplines of archaeology, history of art and architecture, anthropology, linguistics, and history. In their research, they have analyzed all sorts of material evidence, pursuing questions having to do with consumerism and patterns of consumpfion , ideas about objects, visual imagery in popular and elite culture, and technological change. Much ofwhat is valuable in the most suc­ cessful papers is the wealth of detail and precise description they offer, something Africanist scholarship still needs desperately. But if there was any fertile exchange of ideas and perspectives across disciplines at the conference, it is not very much in evidence here. The introductory essay, especially, seems to have been written in iso­ lation, disregarding among other things the problems of identifying cultural and ethnic groupings in Africa. Moreover, it should not be necessary anymore to argue in favor of an “Africa-centered ap­ proach to African material culture” or to expose the false dichotomy of cultural context versus aesthetics and visual imagery (p. 10). Readers can safely pass up the introduction and find in a number of these papers answers to questions they might have about why ob­ jects matter and deserve scrutiny. I focus here on several selected examples, works likely to be of greatest interest to readers of this journal. Philip Ravenhill...

Theoretical study of the dipole-bound anion (HF)2−

It has long been assumed that dipole-bound anionic states possess two properties; (i) the electron binding energy is dominated by the electrostatic electron–dipole interaction, and (ii) the geometrical distortion of the polar molecule upon attachment of a distant electron is negligible. Our results indicate, however, that the dispersion interaction between the loosely bound electron and the electrons of the neutral dimer is as important as the electrostatic electron–dipole stabilization. In addition, the hydrogen bond in (HF)2 is susceptible to a deformation upon attachment of a distant electron. This deformation enhances both the electrostatic and dispersion components of the electron binding energy. The calculated Franck–Condon factors indicate that neutral dimers formed in electron photodetachment experiments may be vibrationally excited in both stiff intramolecular HF stretching modes and soft intermolecular modes. The predicted value of the adiabatic electron detachment energy for (HF)2− is 396 cm−1 and the theoretical photoelectron spectrum is in remarkable agreement with the experimental data of Bowen et al. J. H. Hendricks, H. L. de Clercq, S. A. Lyapustina, and K. H. Bowen, Jr. [J. Chem. Phys. 107, 2962 (1997)].

Identification of Motilin mRNA in the Brain of Man and Rabbit. Conservation of Polymorphism of the Motilin Gene Across Species

Depoortere, I., P. De Clercq, M. Svoboda, L. Bare and T. L. Peeters. Identification of motlin mRNA in the brain of man and rabbit. Conservation of polymorphism of the motlin gene across species. Peptides 18(10) 1497–1503, 1997.—The data regarding the identity of motilin-like immunoreactivity in the central nervous system are controversial. The aim of the present study was to clarify whether motilin mRNA is present in the brain of rabbit and man. Total RNA, prepared from several regions of the rabbit brain, was subjected to RT-PCR aimed at amplifying a 294 bp cDNA fragment of the rabbit motilin precursor. The amplified product was subcloned and sequenced. The sequence showed 7 differences compared to the one reported for the duodenal precursor [1]. However the duodenal precursor from the rabbit used in the present study revealed identical substitutions. One of these, involving amino acid −11 of the signal peptide, was shown to be due to gene polymorphism, as has also been described at this site in man. By radioimmunoassay the highest concentration of motilin (fmol/mg protein) was detected in the hippocampus (4788 ± 295), the lowest in the telencephalon (2127 ± 221). Using a similar approach, but starting from commercial human brain mRNA, the sequence of a comparable cDNA fragment of the human brain motilin precursor was obtained. Its sequence was identical with the one published for the human intestinal precursor [41]. Our study demonstrates that motilin mRNA is present in the brain of man and rabbit. Together with our recent findings of central motilin receptors, they suggest a central role for motilin.

5589615 Process for the production of transgenic plants with increased nutritional value via the expression of modified 2S storage albumins : De Clercq Ann; Krebbers Enno; Vandekerckhove Joacu el; Barreto De Castro Lui; Gander Eugen; Van Montagu Mar Harelbeke, Belgium Assigned to Plant Genetic Systems N V; Brazilian Agricultural Research Organization-Embrapa/Cenarg

5589615 Process for the production of transgenic plants with increased nutritional value via the expression of modified 2S storage albumins : De Clercq Ann; Krebbers Enno; Vandekerckhove Joacu el; Barreto De Castro Lui; Gander Eugen; Van Montagu Mar Harelbeke, Belgium Assigned to Plant Genetic Systems N V; Brazilian Agricultural Research Organization-Embrapa/Cenarg

Treatment of progressive multifocal leukoencephalopathy (PML) with cidofovir in an AIDS patient: R. Snoeck 1, S. De Wit 2, C. Rossi 2, B. Dachy 2, E. O'Doherty 2, L. Naesens 1, J. Balzarini 1. E. De Clercq 1, S. Goldman 3 and N. Clumeck 21Rega Institute for Medical Research, K.U.Leuven, Leuven; 2St. Pierre Hospital, Brussels; 3Erasmus Hospital, Brussels, Belgium

Treatment of progressive multifocal leukoencephalopathy (PML) with cidofovir in an AIDS patient: R. Snoeck 1, S. De Wit 2, C. Rossi 2, B. Dachy 2, E. O'Doherty 2, L. Naesens 1, J. Balzarini 1. E. De Clercq 1, S. Goldman 3 and N. Clumeck 21Rega Institute for Medical Research, K.U.Leuven, Leuven; 2St. Pierre Hospital, Brussels; 3Erasmus Hospital, Brussels, Belgium

Synthesis, biological and physical evaluation of some novel glycolipid analogues: W.P. Blackaby 1, C. McGuigan 1, G.S. Attard 2, N. Mahmood 3, A.J. Hay 3, J. Balzarini 4 and E. De Clercq 4 1Welsh School of Pharmacy, University of Wales Cardiff, Cardiff CF1 3XF; 2University of Southampton, Southampton S09 5NH; 3MRC Collaborative Center, London W1N 4AL, United Kingdom; 4Rega Institute

Synthesis, biological and physical evaluation of some novel glycolipid analogues: W.P. Blackaby 1, C. McGuigan 1, G.S. Attard 2, N. Mahmood 3, A.J. Hay 3, J. Balzarini 4 and E. De Clercq 4 1Welsh School of Pharmacy, University of Wales Cardiff, Cardiff CF1 3XF; 2University of Southampton, Southampton S09 5NH; 3MRC Collaborative Center, London W1N 4AL, United Kingdom; 4Rega Institute

Mechanism of anti-HIV action of masked alaninyl 2′,3′-dideoxy-2′,3′-didehydrothymidine 5′-monophosphate derivatives: J. Balzarini 1, H. Egberink 2, K. Hartmann 3, A. Karlsson 4, C.-F. Perno 5, D. Cahard 6, L. Naesens 1, H. Thormar 7, E. De Clercq 1 and C. McGuigan 6 1Rega Institute for Medical Research, K.U.Leuven, Leuven, Belgium; 2Institute of Virology, Veterinary Faculty, Utrecht, The Netherlands; 3Medizinische Tierklinik,

Mechanism of anti-HIV action of masked alaninyl 2′,3′-dideoxy-2′,3′-didehydrothymidine 5′-monophosphate derivatives: J. Balzarini 1, H. Egberink 2, K. Hartmann 3, A. Karlsson 4, C.-F. Perno 5, D. Cahard 6, L. Naesens 1, H. Thormar 7, E. De Clercq 1 and C. McGuigan 6 1Rega Institute for Medical Research, K.U.Leuven, Leuven, Belgium; 2Institute of Virology, Veterinary Faculty, Utrecht, The Netherlands; 3Medizinische Tierklinik,

S-Adenosylhomocysteine hydrolase inhibitors as potent anti-RNA viral agents : A. Matsuda, aS. Shuto, aT. Obara, bS. Shigeta, cand E. De Clercq. d Faculty of Pharmaceutical Sciences, Hokkaido University, a Sapporo 060, Japan, Institute for Life Science Research, Asahi Chemical Industry Co. Ltd. Ohito, b Sizuoka 410-23, Japan, Department of Microbiology, Fukushima Medical College, c Fukushima 960-12, Japan, and Rega Institute

S-Adenosylhomocysteine hydrolase inhibitors as potent anti-RNA viral agents : A. Matsuda, aS. Shuto, aT. Obara, bS. Shigeta, cand E. De Clercq. d Faculty of Pharmaceutical Sciences, Hokkaido University, a Sapporo 060, Japan, Institute for Life Science Research, Asahi Chemical Industry Co. Ltd. Ohito, b Sizuoka 410-23, Japan, Department of Microbiology, Fukushima Medical College, c Fukushima 960-12, Japan, and Rega Institute

ADA, a potential anti-HIV drug: M. Witvrouw 1, M. Vandevelde 2, J.-P. Tassignon 3, J.-C. Schmit 1, J. Desmyter 1 and E. De Clercq 1 1Rega Institute for Medical Research, K.U.Leuven, Leuven, Belgium; 2Hubriphar SPRL, Brussels, Belgium; 3Tassignon & Partners S.A., Brussels, Belgium

ADA, a potential anti-HIV drug: M. Witvrouw 1, M. Vandevelde 2, J.-P. Tassignon 3, J.-C. Schmit 1, J. Desmyter 1 and E. De Clercq 1 1Rega Institute for Medical Research, K.U.Leuven, Leuven, Belgium; 2Hubriphar SPRL, Brussels, Belgium; 3Tassignon & Partners S.A., Brussels, Belgium

The same point mutation within region II of the herpes simplex virus type 1 (HSV-1) DNA polymerase gene confers resistance to foscarnet (PFA) and the phosphonylmethoxyethyl (PME) derivatives of adenine (PMEA) and 2,6-diaminopurine (PMEDAP): G. Andrei, R. Snoeck, E. De Clercq, P. Fiten and G. Opdenakker Rega Institute for Medical Research, K.U.Leuven, Leuven, Belgium

The same point mutation within region II of the herpes simplex virus type 1 (HSV-1) DNA polymerase gene confers resistance to foscarnet (PFA) and the phosphonylmethoxyethyl (PME) derivatives of adenine (PMEA) and 2,6-diaminopurine (PMEDAP): G. Andrei, R. Snoeck, E. De Clercq, P. Fiten and G. Opdenakker Rega Institute for Medical Research, K.U.Leuven, Leuven, Belgium

An application of MTT-colorimetric assay for the screening of anti-adenovirus agents: E. Kodama 1,2, S. Shigeta 2, T. Suzuki 3, and E. De Clercq 4. 1 Dept. of Pediatrics, University of Alabama at Birmingham, Ala., USA, 2 Dept. of Microbiology, and 3 2nd Dept. of Pathology, Fukushima Medical College, Fukushima, Japan, and 4 Rega Institute for Medical Research, Katholieke Universiteit

An application of MTT-colorimetric assay for the screening of anti-adenovirus agents: E. Kodama 1,2, S. Shigeta 2, T. Suzuki 3, and E. De Clercq 4. 1 Dept. of Pediatrics, University of Alabama at Birmingham, Ala., USA, 2 Dept. of Microbiology, and 3 2nd Dept. of Pathology, Fukushima Medical College, Fukushima, Japan, and 4 Rega Institute for Medical Research, Katholieke Universiteit