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expert in this field, had already criticized Buck's research a year before, and resigned because his warnings were not taken seriously. Van
Boeckel had also been working on synthesis of phosphate methylated DNA, and knew how difficult it was to make such DNA-strands. A year before Buck's downfall, he came to the conclusion that Buck's longer strands could not be pure, because Van Boeckel's research-assistant Kuijpers noticed that even a short phosphate methylated DNA wasn't stable. In May 1989 he invited one of Buck's research assistants to test their material on
228:. In these reviews he gives also a description and explanation of the chemical and corresponding biochemical results of the methylphosphotriester DNA, RNA and related systems. This contribution that is mainly based on the work at Eindhoven also consists of new insights in solid-phase synthesis, B-Z transition, and methyl transfer reactions connected with replicational and transcriptional silencing. Special attention is given to the effect of phosphate shielding on duplex stability. Models based on
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the proceedings and their conclusion (30 August 1990) was, that no phosphate methylated DNA could be traced. Also the committee reproached Buck for not paying attention to criticism from within his faculty. As a result, Buck was dismissed as dean of the faculty. Goudsmit was requested to test the antisense material once again, but his enthusiasm had cooled, and Buck could not produce the pure phosphate methylated DNA in time.
299:, a Dutch pharmaceutical company. The measurement showed that the test material was not at all pure, but Buck refused to accept this fact. When Van Boeckel showed Buck a draft of the publication of his own research at the end of 1989, it resulted in a confrontation in which the university chose Buck's side. Van Boeckel and Kuijpers were ordered to stop their research, because "it was too expensive and not productive".
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pure enough. Therefore, a third committee investigated the work of
Goudsmit and his group as well. The committee concluded that Goudsmit had not checked the quality of Buck's material. Also they saw shortcomings in the interpretation and presentation of the results. The committee concluded that Goudsmit's research had been scientifically inadequate. Goudsmit did not go in appeal and could continue his work.
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phosphorus appeared of importance for intra- and intermolecular dynamics. These modified DNAs mimicked the behavior of natural DNA in the absence of stabilizing factors as salts, proteins, and medium factors. In fact a high site-specific hybridization affinity was obtained with complementary natural DNA. In dependence of the bases,
109:. Because there was no chair for Theoretical Chemistry and Biochemistry he gave lectures in organic chemistry, physical organic chemistry, theoretical organic chemistry, biochemistry and biotechnology. From 1988 to 1991 he was Dean of the Chemical Faculty. For his scientific contributions he became a member of the
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The doubts and criticism following the publication in
Science led to a heated public debate in several Dutch newspapers and science magazines, and the university eventually acknowledged that the purity of the phosphate methylated DNA was still to be investigated. A committee was formed to investigate
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Although Jaap
Goudsmit generally was regarded as a victim in the affair, half a year later a journalist of a leading newspaper questioned his role in the débâcle. Goudsmit had reported the inhibition of HIV-replication, which was questionable, given the fact that the phosphate methylated DNA was not
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professor Van Boom, expert in the field of DNA synthesis, said in a leading Dutch newspaper, that pure phosphate methylated DNA is very difficult to produce, and easily contaminated. Six days after the publication internal criticism came to the surface. Buck colleague, professor Van
Boeckel, also an
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On the eve of the publication, the
University of Eindhoven made the news public. It resulted in excited media attention in the Netherlands, and under the pressure Buck publicly stated that he assumed that AIDS would be of the past in a couple of years, although it was agreed not to make such claims.
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created short phosphate methylated DNA-fragments, and considered the possibility of using this as a means of influencing DNA-replication. Buck's research group focused on the use of this phosphate methylated DNA, in particular because of its neutral electrical properties. In several publications the
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emission spectra and absolute radiative lifetimes of formaldehyde. Further he investigated deviations of the
Woodward-Hoffmann rules as the photochemical -OH shift in 2-propen-1-ol. Here the stereochemical outcome is determined by relaxation of the excited double bond. A thermal study of the cis--H
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To this day, however, nobody produced pure phosphate methylated DNA strands in the quality
Goudsmit required. All the efforts from Miller, Van Boeckel and Buck resulted in short instable fragments. Recent researches in this field are based on methyl phosphonate or phosphorothioate DNA. At present
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of phosphate-methylated DNAs and RNAs. Methylphosphotriester DNAs were synthesized with 2-12 bases. Neutralization of the charge of the phosphate linkages by (specific) methylation resulted in methylphosphotriester DNAs with very exclusive (bio)chemical properties. The introduction of chirality at
191:
which shows a number of unique properties. The significance of this geometrical change has been demonstrated in the conformational transmission in DNA for the B-Z transition with alternating CpG units under selective phosphate shielding. This change in geometry of phosphorus was also applicable on
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in 1979. During his scientific career he published more than 300 scientific papers spread over a large area of the chemical field. Under his supervision 43 chemical engineers obtained their PhD. The end of his career came prematurely because of a publication in
Science in 1990 regarding a possible
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A second investigating committee reported at the end of the year that the presentation of the results in
Science bordered on fraud. The report also said that Buck's behaviour in his group was impermissibly harsh at times. The committee concluded that it disqualified him as a research leader. As a
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Henk Buck never accepted the outcome of this controversy. He persisted in his opinion that he could produce sufficiently pure phosphate methylated DNA. In several interviews he said that he felt that he has been pilloried for making a sincere mistake. He published two articles in the scientific
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measurements of phosphoranyl radicals with phosphorus in different geometries as the tetrahedral and the trigonal bipyramidal configuration with the unpaired electron in an equatorial or axial orientation. His contribution to the theoretical organic chemistry was based on
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Broeders, N.L.H. et al. (1990)"A 400- and 600- MHz H NMR conformational study on nucleoside cyclic 3',5'P-TBP systems. Conformational transmission induces diequatorial orientation of the 3',5'-dioxaphosphorinane ring in a nonchair conformation",
272:. Jaap Goudsmit required longer DNA-strands, though, than the ones Buck was testing so far, so a new synthesis route was developed. Jaap Goudsmit tested the new strands on samples of HIV and reported the inhibition of the virus replication.
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DNA could be synthesized for pyrimidine bases in which the chirality of phosphorus was decisive. Phosphate methylation also gave the possibility to synthesize a self-complementary left-handed Z-DNA mini duplex.
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Aagaard, O.M. et al. (1990) "Intermolecular effects on the radiogenic formation of electron-capture phosphorus-centered Journalradicals A single-crystal ESR study of diastereoisomeric precursors",
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Buck, H.M. (2007) "The Chemical and Biochemical Properties of Methylphosphotriester DNA and RNA in Comparison with their Corresponding Methylphosphonates. A Dynamic Model Description",
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Afterwards he explained, he deliberately had said this to raise more funds for his research, although much later he defended himself by saying that he was provoked by the reporter.
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Van Pelt, P. et al. (1976) "Proton acid catalyzed hydride transfer from alkanes to methylated benzyl cations. Part III: Solvated alkanes as Hydrogen-donating intermediates",
421:
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Kuijpers, W.H.A. e.a. (1990) "Synthesis of well-defined phosphate-methylated DNA fragments: the application of potassium carbonate in methanol as deprotecting agent",
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European Patent entitled Poly(deoxyribonucleotides), pharmaceutical compositions, use and preparation of the poly(deoxyribonucleotides) München 09-06-1993, Patent NO.
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Donkersloot, M.C.A. et al.(1981) "The hydride-donation reaction of reduced nicotinamide adenine dinucleotide. 2.MINDO/3 and STO-3G calculations on the role of the CONH
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calculations and recent density functional ab initio calculations support the impact of phosphate shielding at the various levels of stability of the DNA duplex.
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Miller P.S. e.a (1971) "Syntheses and properties of adenine and thymine nucleoside alkyl phosphotriesters, the neutral analogs of dinucleoside monophosphates."
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150:. The latter process is controlled by the out-of-plane orientation of the carboxamide group. In the field of physical chemistry his work was directed on
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of organophosphorus radicals and the hybridization affinity of methylphosphotriester DNA and RNA. The latter subject is published as review articles in
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At home without any academic support he wrote several articles based on quantum chemical calculations focused on the dynamics of organic reactions,
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Vekemans, J.A.J.M. et al. (1991) "NADH model mediated reduction of C=N substrates: enantio-selective synthesis of D-and L-phenylglycinates",
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Zamecnik P.C. e.a. (1978) "Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide."
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group was introduced as substitute for O in the study of intermediates for conformational transmission. This also resulted in the
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Dormans, G.J.M. et al. (1984) "A quantum chemical study on the mechanism of a photochemical {1,3]-OH shift in 2-propen-1-ol",
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Buck, H.M. e.a. (1990) "Phosphate-Methylated DNA Aimed at HIV-1 RNA Loops and Integrated DNA Inhibits Viral Infectivity",
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in which he tries to retrace what happened, and he goes as far as to claim that the investigating committees were wrong.
260:-infections in those days, commercial interests and patent rights led to the decision to cooperate with the virologist
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replication had to be retracted, because it was based on flawed research, he accepted early retirement in 1990. (see
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at the university in Theoretical Organic Chemistry in 1964. For his research he received the Golden Medal of the
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Hagendijk, R. en Meeus, J. (1993) "Blind faith: fact, fiction and fraud in public controversy over science".
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CI calculation of single vibronic level fluorescence emission spectra and absolute radiative lifetimes of H
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in 1967. In 1970 he was appointed professor of Physical Organic Chemistry and Organic Chemistry at the
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Moody, H.M. e.a. (1990) "Inhibition of HIV-1 Infectivity by Phosphate-Methylated DNA: Retraction",
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Rozendaal, S. (1992) "Barbertje wil weer werken. Waarom AIDS-onderzoeker Henk Buck moest hangen".
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Buck, H.M. (2004) "The Chemical and Biochemical Properties of Methylphosphotriester DNA",
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or has been extensively edited by the subject or by someone connected to the subject
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Doubts raised immediately after the article appeared in Science. The next day, the
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the biochemical dynamics of cAMP. Because of the importance of shielding, the OCH
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as the pentamethylbenzyl cation and the chiral induction with the redox couple
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Proceedings of the National Academy of Sciences of the United States of America
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1,3-pentadiene. Kinetic isotope effect and vibrationally assisted tunneling",
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Koole, L.H. et al. (1987) "A parallel right-handed duplex of the hexamer d(T
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is generally regarded as the founder of this technique, but already in 1971
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424:(in Dutch). Nederlandse Omroep Stichting. 5 December 2023. Archived from
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326:(2008) only one antisense medication exists, based on phosphorothioate
179:. An important aspect of this project was based on the possibility of
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Dormans, G.J.M. et al. (1984) " Mechanism of the thermal -H shift in
422:"Henk Buck, bekend van Buck-affaire, overleden op 93-jarige leeftijd"
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shifts in 1,3-pentadiene showed the effect of vibrationally assisted
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cure for cancer that had to be retracted because of flawed research.
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Members of the Royal Netherlands Academy of Arts and Sciences
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His research in Leiden and later in Eindhoven was focused on
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Public Understanding of Science, Vol. 2, No. 4, pp. 391-415.
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In the mid-80s Henk Buck focused his research on the use of
402:(in Dutch). Royal Netherlands Academy of Arts and Sciences
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The publication in Science therefore had to be retracted.
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transition in methylated DNA. A quantum-chemical study",
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Academic staff of the Eindhoven University of Technology
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CI calculation of the radiationless transition of the (
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After a publication in Science about the inhibition of
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in the nearly 100% stereospecific hydride transfer to
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and ab initio calculations of single vibronic level
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It may need editing to conform to Knowledge (XXG)'s
661:, 13 April 1990: Vol. 248. no. 4952, pp. 208 - 212.
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81:(7 February 1930 – 27 November 2023) was a Dutch
159:calculations of the radiationless transition of
46:policy. There may be relevant discussion on the
253:selectivity and duplex forming were reported.
111:Royal Netherlands Academy of Arts and Sciences
8:
226:Nucleosides, Nucleotides & Nucleic Acids
754:Nucleosides, Nucleotides and Nucleic Acids
746:Nucleosides, Nucleotides and Nucleic Acids
320:Nucleosides, Nucleotides and Nucleic Acids
244:DNA as an inhibitor of virus replication.
707:Journal of the American Chemical Society.
440:Journal of the American Chemical Society,
66:Learn how and when to remove this message
642:Journal of the American Chemical Society
594:Journal of the American Chemical Society
559:Journal of the American Chemical Society
542:Journal of the American Chemical Society
483:Journal of the American Chemical Society
470:Journal of the American Chemical Society
310:result, Buck accepted early retirement.
89:on 7 February 1930. Buck studied at the
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341:on 27 November 2023, at the age of 93.
640:T) with phosphate triester linkages",
107:University of Technology in Eindhoven
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175:A special topic in his research was
126:as the homogeneous catalysis of the
799:Academic staff of Leiden University
103:Royal Netherlands Chemical Society
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580:European Journal of Biochemistry
515:Van Dijk, J.M.F. et al. (1978) "
494:Van Dijk, J.M.F. et al. (1978) "
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570:Van Lier, J.J.C. et al. (1983)
529:Journal of the Chemical Physics
504:Journal of the Chemical Physics
468:group in enzymatic reactions",
172:in this geometric orientation.
275:The results were published in
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236:The Buck-Goudsmit controversy
215:The Buck-Goudsmit controversy
183:(IV) to accommodate a fifth
784:20th-century Dutch chemists
748:, Vol. 23, pp. 1833 - 1847.
502:pi)state of formaldehyde",
360:21-10-1992, pp. 96–100
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177:organophosphorus chemistry
644:, Vol. 109, pp. 3916-3921
596:, Vol. 106, pp. 7475-7482
561:, Vol. 106, pp. 3253-3258
544:, Vol. 106, pp. 1213-1216
472:, Vol. 103, pp. 6554-6558
455:, Vol.2, pp. 949–952
16:Dutch chemist (1930–2023)
794:Leiden University alumni
724:, Vol. 18, pp. 5197-5205
679:, Vol. 250, pp. 125-126.
531:, Vol. 70, pp. 2854-2858
506:, Vol. 69, pp. 2462-2473
453:Thetrahedron: A symmetry
382:"Death notice Henk Buck"
295:equipment in the lab of
756:, Vol. 26, pp. 205-222.
485:, Vol. 112, pp. 938-944
266:Academic Medical Center
222:electron spin resonance
152:electron spin resonance
734:Hagendijk (1993) p.401
722:Nucleic Acids Research
694:January;75(1)pp. 280-4
442:Vol. 98, pp. 5864-5870
93:where he received his
809:People from Dordrecht
582:, Vol. 132, pp. 55-62
256:The strong growth of
187:under formation of a
44:neutral point of view
270:Amsterdam University
91:University of Leiden
709:Vol 93, pp. 6657-65
428:on 7 December 2023.
279:on April 13, 1990.
230:molecular mechanics
189:trigonal bipyramid
97:in 1959. He got a
288:Leiden University
124:organic chemistry
85:. He was born in
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56:January 2011
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779:2023 deaths
774:1930 births
400:"H.M. Buck"
388:(in Dutch).
768:Categories
365:References
332:Fomivirsen
181:phosphorus
99:lectorship
517:Ab initio
496:Ab initio
318:magazine
242:antisense
198:synthesis
170:tunneling
157:Ab initio
128:oxidation
87:Dordrecht
79:Henk Buck
48:talk page
358:Elsevier
203:parallel
140:NADH-NAD
118:Research
677:Science
659:Science
610:0358657
406:14 July
345:Sources
339:Tilburg
297:Organon
277:Science
264:of the
144:ketones
185:ligand
148:imines
34:is an
211:HIV-1
523:CO(A
408:2015
293:HPLC
146:and
555:cis
527:)",
386:NRC
268:of
258:HIV
130:of
95:PhD
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638:P
636:T
634:P
632:T
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576:Z
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572:B
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