Williams, David M. , Dr

Dr David M. Williams

School of Mathematical and Physical Sciences

Reader in Chemical Biology

d.m.williams@sheffield.ac.uk
+44 114 222 9502

Dainton Building

Full contact details

Dr David M. Williams
School of Mathematical and Physical Sciences
Dainton Building
13 Brook Hill
��«Ӱҵ
S3 7HF

Profile

Dr. Williams obtained a BSc in Chemistry from the University of Liverpool in 1985, which was followed by a PhD from the same institution in 1988. From 1988, he was a Postdoctoral Research Fellow at the Max-Planck Institute for Experimental Medicine in Göttingen and from 1992-1995 at the MRC Laboratory of Molecular Biology in Cambridge.

In 1995 he became a demonstrator at the University of ��«Ӱҵ. In 1999 he became a lecturer and in 2006 a senior lecturer. In 2014 he was promoted to Reader.

Research interests

Our main areas of research are in the synthesis of modified nucleosides and nucleotides and their applications.

Currently we are interested in the chemical synthesis of 5'-triphosphates of base-modified, nucleoside analogues that have altered base pairing specificities. We are studying the incorporation of these analogues into DNA by polymerase enzymes in order to gain an insight into the role of base pairing during DNA replication and DNA mutagenesis.

Exposure to alkylating agents can lead to the formation of highly toxic O6-alkylguanine lesions within DNA. We have developed chemical methodology for the preparation of oligodeoxyribonucleotides containing a variety of O6-alkylguanine analogues and these are being used to study DNA recognition and repair by the human protein O6-methylguanine-DNA methyltransferase (MGMT) and the alkyltransferase-like protein Atl1.

Other areas of interest include the use SELEX for the design of nucleic acid-based ligands and catalysts containing chemically synthesised imidazolyl and amino modified nucleotides of dUTP and 7-deazadATP, studying the structural properties of nucleic acids containing modified pyrimidine and purine bases and the design and synthesis of modified oligodeoxyribonucleotides for DNA-DNA and DNA-protein cross-linking.

Publications

Books

Blackburn GM (2006) Nucleic Acids in Chemistry and Biology. Royal Society of Chemistry.

Journal articles

Gil da Costa RM, Povey A, Medeiros-Fonseca B, Ramwell C, O'Driscoll C, Williams D, Chr. B. Hansen H, Holm Rasmussen L, Fletcher MT, O'Connor P , Bradshaw RHW et al (2024) . Environmental Research, 119274-119274.
Dutson C, Allen E, Thompson MJ, Hedley JH, Murton HE & Williams DM (2021) . Molecules, 26(8).
Abdu K, Aiertza MK, Wilkinson OJ, Senthong P, Craggs TD, Povey AC, Margison GP & Williams DM (2020) . Nucleosides, Nucleotides & Nucleic Acids.
Hodskinson MR, Bolner A, Sato K, Kamimae-Lanning AN, Rooijers K, Witte M, Mahesh M, Silhan J, Petek M, Williams DM , Kind J et al (2020) . Nature, 579(7800), 603-608.
Dexter HR, Allen E & Williams DM (2018) . Tetrahedron Letters, 59(49), 4323-4325.
Abdelhady RA, Barran PE, Williams DM & Povey AC (2017) . Cancer Research, 77(13_Supplement), 4242-4242.
Räz MH, Dexter HR, Millington CL, Van Loon B, Williams DM & Sturla SJ (2016) . Chem Res Toxicol, 29(9), 1493-1503.
Wyss LA, Nilforoushan A, Williams DM, Marx A & Sturla SJ (2016) . Nucleic Acids Res, 44(14), 6564-6573.
Zhang F, Tsunoda M, Kikuchi Y, Wilkinson O, Millington CL, Margison GP, Williams DM & Takénaka A (2014) . Acta Crystallogr D Biol Crystallogr, 70(Pt 6), 1669-1679.
Zhang F, Tsunoda M, Suzuki K, Kikuchi Y, Wilkinson O, Millington CL, Margison GP, Williams DM, Czarina Morishita E & Takénaka A (2013) . Nucleic Acids Res, 41(10), 5524-5532.
Abdu K & Williams DM (2013) . International Journal of Chemical Engineering and Applications, 69-73.
Senthong P, Millington CL, Wilkinson OJ, Marriott AS, Watson AJ, Reamtong O, Eyers CE, Williams DM, Margison GP & Povey AC (2013) . Nucleic Acids Res, 41(5), 3047-3055.
Wilkinson OJ, Latypov V, Tubbs JL, Millington CL, Morita R, Blackburn H, Marriott A, McGown G, Thorncroft M, Watson AJ , Connolly BA et al (2012) . Proc Natl Acad Sci U S A, 109(46), 18755-18760.
Abdu K, Aiertza MK, Wilkinson OJ, Grasby JA, Senthong P, Povey AC, Margison GP & Williams DM (2012) . Chem Commun (Camb), 48(91), 11214-11216.
Beddows A, Patel N, Finger LD, Atack JM, Williams DM & Grasby JA (2012) . Chem Commun (Camb), 48(71), 8895-8897.
Latypov VF, Tubbs JL, Watson AJ, Marriott AS, McGown G, Thorncroft M, Wilkinson OJ, Senthong P, Butt A, Arvai AS , Millington CL et al (2012) . Molecular Cell, 47(1), 50-60.
Patel N, Atack JM, Finger LD, Exell JC, Thompson P, Tsutakawa S, Tainer JA, Williams DM & Grasby JA (2012) . Nucleic Acids Res, 40(10), 4507-4519.
Millington CL, Watson AJ, Marriott AS, Margison GP, Povey AC & Williams DM (2012) . Nucleosides Nucleotides Nucleic Acids, 31(4), 328-338.
Williams D (2010) Understanding the cosmos. Chemistry and Industry (London)(15).
Bao G, Clifton M, Hoette TM, Mori K, Deng S-X, Qiu A, Viltard M, Williams D, Paragas N, Leete T , Kulkarni R et al (2010) . Nature Chemical Biology, 6(8), 602-609.
Magat Juan EC, Shimizu S, Ma X, Kurose T, Haraguchi T, Zhang F, Tsunoda M, Ohkubo A, Sekine M, Shibata T , Millington CL et al (2010) . Nucleic Acids Res, 38(19), 6737-6745.
Plant A, Thompson P & Williams DM (2009) . J Org Chem, 74(13), 4870-4873.
Tubbs JL, Latypov V, Kanugula S, Butt A, Melikishvili M, Kraehenbuehl R, Fleck O, Marriott A, Watson AJ, Verbeek B , McGown G et al (2009) . NATURE, 459(7248), 808-813.
Li JY, Paragas N, Ned RM, Qiu A, Viltard M, Leete T, Drexler IR, Chen X, Sanna-Cherchi S, Mohammed F , Williams D et al (2009) . Developmental Cell, 16(1), 35-46.
Plant A, Thompson P & Williams DM (2008) . J Org Chem, 73(10), 3714-3724.
Haraguchi T, Shimizu S, Ma X, Kurose T, Juan ECM, Ohkubo A, Sekine M, Shibata T, Millington CL & Williams DM (2008) (52), 127-128.
Millington CL, Shibata T, Margison G & Williams DM (2008) Novel post DNA synthesis chemistry and biological evaluation of O-6-alkylguanine-containing oligodeoxyribonucleotides. CHEMISTRY OF NUCLEIC ACID COMPONENTS, 10, 133-136.
Hornillo-Araujo AR, Burrell AJM, Aiertza MK, Shibata T, Hammond DM, Edmont D, Adams H, Margison GP & Williams DM (2007) . Nucleosides Nucleotides Nucleic Acids, 26(8-9), 1099-1102.
Shibata T, Buurma NJ, Brazier JA, Thompson P, Haq I & Williams DM (2006) . Chem Commun (Camb)(33), 3516-3518.
Hornillo-Araujo AR, Burrell AJM, Aiertza MK, Shibata T, Hammond DM, Edmont D, Adams H, Margison GP & Williams DM (2006) . Org Biomol Chem, 4(9), 1723-1729.
Ma X, Kurose T, Juan ECM, Shibata T, Williams DM & Takenaka A (2006) (50), 213-214.
Pearson SJ, Wharton S, Watson AJ, Begum G, Butt A, Glynn N, Williams DM, Shibata T, Santibanez-Koref MF & Margison GP (2006) . NUCLEIC ACIDS RES, 34(8), 2347-2354.
Shibata T, Glynn N, McMurry TBH, McElhinney RS, Margison GP & Williams DM (2006) . Nucleic Acids Res, 34(6), 1884-1891.
Shibata T & Williams DM (2005) . Nucleic Acids Symp Ser (Oxf)(49), 23-24.
Brazier JA, Shibata T, Townsley J, Taylor BF, Frary E, Williams NH & Williams DM (2005) . Nucleic Acids Res, 33(4), 1362-1371.
Marsh AJ, Williams DM & Grasby JA (2004) . Org Biomol Chem, 2(14), 2103-2112.
Sidorov AV, Grasby JA & Williams DM (2004) . Nucleic Acids Res, 32(4), 1591-1601.
Hammond DM, Edmont D, Hornillo-Araujo AR & Williams DM (2003) . Org Biomol Chem, 1(23), 4166-4172.
Harris VH, Smith CL, Cummins WJ, Hamilton AL, Hornby DP & Williams DM (2003) . Org Biomol Chem, 1(12), 2070-2074.
Harris VH, Smith CL, Jonathan Cummins W, Hamilton AL, Adams H, Dickman M, Hornby DP & Williams DM (2003) . J Mol Biol, 326(5), 1389-1401.
Araujo ARH, Edmont D & Williams DM (2002) Synthesis and applications of a tricyclic analogue of N-6-methoxy-2,6-diamino-2 '-deoxyriboside. CHEMISTRY OF NUCLEIC ACID COMPONENTS, 5, 328-331.
Harris VH, Smith C, Cummins J, Hamilton A, Hornby DP & Williams DM (2002) DNA replication with the mutagenic nucleotide dPTP; Effects of tautomerism on nucleotide incorporation. CHEMISTRY OF NUCLEIC ACID COMPONENTS, 5, 215-220.
Brazier JA & Williams DM (2002) Synthesis and applications of C5-amino modified 2 '-deoxyuridines. CHEMISTRY OF NUCLEIC ACID COMPONENTS, 5, 221-224.
Gourlain T, Sidorov A, Mignet N, Thorpe SJ, Lee SE, Grasby JA & Williams DM (2001) . Nucleic Acids Res, 29(9), 1898-1905.
Lee SE, Sidorov A, Gourlain T, Mignet N, Thorpe SJ, Brazier JA, Dickman MJ, Hornby DP, Grasby JA & Williams DM (2001) . Nucleic Acids Res, 29(7), 1565-1573.
Cain SA, Williams DM, Harris V & Monk PN (2001) . Protein Eng, 14(3), 189-193.
Cain SA, Ratcliffe CF, Williams DM, Harris V & Monk PN (2000) . J Immunol Methods, 245(1-2), 139-145.
Edmont D & Williams DM (2000) A new and versatile synthesis of 5-substituted pyrrolo[2,3-d]pyrimidines. TETRAHEDRON LETT, 41(44), 8581-8585.
Lee SE, Vyle JS, Williams DM & Grasby JA (2000) Novel syntheses of (Z)-alkene and alkane base-modified nucleosides. TETRAHEDRON LETT, 41(2), 267-270.
Lee SE, Mignet N, Vyle JS, Whetton L, Grasby JA & Williams DM (1999) The synthesis of modified 5-(aminoalkyl)- and 5-(aminoalkenyl)uridine 5 '-triphosphates. CHEMISTRY OF NUCLEIC ACID COMPONENTS, 2, 35-38.
Harris VH, Hamilton A, Williams DM & Hornby DP (1999) Studying the function of methyltransferases using nucleotide analogue based random mutagenesis. CHEMISTRY OF NUCLEIC ACID COMPONENTS, 2, 209-212.
Hill F, Loakes D, Smith CL, Williams DM & Brown DM (1999) Synthesis and polymerase incorporation properties of a tricyclic pyrrolopyrimidine related to N-6-hydroxy-2 '-deoxyadenosine. NUCLEOSIDES & NUCLEOTIDES, 18(4-5), 573-574.
Jakeman DL, Bernstein B, Hol W, Williams DM, Williamson MP & Blackburn GM (1999) Highly potent bisphosphonate ligands for phosphoglycerate kinase and protein binding studies. PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS, 146, 533-536.
Williams DM, Jakeman DL, Vyle JS, Williamson MP & Blackburn GM (1998) . Bioorg Med Chem Lett, 8(18), 2603-2608.
Bernstein BE, Williams DM, Bressi JC, Kuhn P, Gelb MH, Blackburn GM & Hol WGJ (1998) A bisubstrate analog induces unexpected conformational changes in phosphoglycerate kinase from Trypanosoma brucei. J MOL BIOL, 279(5), 1137-1148.
Moriyama K, Williams DM, Loakes D, Brown DM, Hayatsu H & Negishi K (1998) Properties of mutagenic pyrimidine analogue, P(39), 245-246.
Hill F, Williams DM, Loakes D & Brown DM (1998) . Nucleic Acids Research, 26(5), 1144-1149.
Williams DM, Loakes D & Brown DM (1998) . Journal of the Chemical Society - Perkin Transactions 1(21), 3565-3570.
Williams DM, Yakovlev DY & Brown DM (1997) . Journal of the Chemical Society - Perkin Transactions 1(8), 1171-1178.
Negishi K, Williams DM, Inoue Y, Moriyama K, Brown DM & Hayatsu H (1997) . Nucleic Acids Research, 25(8), 1548-1552.
Zaccolo M, Williams DM, Brown DM & Gherardi E (1996) . Journal of Molecular Biology, 255(4), 589-603.
Williams DM, Jakeman DL, Vyle JS, Williamson MP & Blackburn GM (1996) Synthesis and kinetic studies of bisubstrate analogues of phosphoglycerate kinase. COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS, 61, S88-S91.
Williams DM & Brown DM (1995) . Cheminform1522-2667(10), 1225-1231.
Negishi K, Williams DM, Inoue Y, Iimura T, Katahira M, Kanazawa H, Uesugi S, Hayatsu H & Brown MD (1995) Mechanism of mutagenesis induced by cytosine analogs bearing N(4)-substitutions. Nucleic Acids Symposium Series(34), 231-232.
Williams DM & Brown DM (1995) . Journal of the Chemical Society, Perkin Transactions 1(10), 1225-1225.
Aurup H, Siebert A, Benseler F, Williams D & Eckstein F (1994) Translation of 2'-modified mRNA in vitro and in vivo.. Nucleic Acids Research, 22(23), 4963-4968.
Williams DM & Brown DM (1993) . Collection of Czechoslovak Chemical Communications, 58(s1), 41-43.
Aurup H, Williams DM & Eckstein F (1992) . Biochemistry, 31(40), 9636-9641.
Benseler F, Williams DM & Eckstein F (1992) . Nucleosides and Nucleotides, 11(7), 1333-1351.
Williams DM, Pieken WA & Eckstein F (1992) . Proc Natl Acad Sci U S A, 89(3), 918-921.
Williams DM, Benseler F & Eckstein F (1991) . Biochemistry, 30(16), 4001-4009.
Pieken WA, Olsen DB, Williams DM, Aurup H, Benseler F & Eckstein F (1991) INFLUENCE OF 2'-MODIFICATIONS ON THE STRUCTURE AND FUNCTION OF HAMMERHEAD RIBOZYMES, 372(9), 731-731.
Pieken WA, Olsen DB, Aurup H, Williams DM, Heidenreich O, Benseler F & Eckstein F (1991) Structure-function relationship of hammerhead ribozymes as probed by 2'-modifications.. Nucleic Acids Symp Ser(24), 51-53.
Cosstick R, Li X, Tuli DK, Williams DM, Connolly BA & Newman PC (1990) Molecular recognition in the minor groove of the DNA helix. Studies on the synthesis of oligonucleotides and polynucleotides containing 3-deaza-2'-deoxyadenosine. Interaction of the oligonucleotides with the restriction endonuclease EcoRV.. Nucleic Acids Res, 18(16), 4771-4778.
Newman PC, Connolly BA, Cosstick R, Seela F & Williams DM (1990) . Biochemistry, 29(42), 9902-9910.
Newman PC, Nwosu VU, Connolly BA, Williams DM, Cosstick R & Seela F (1990) . Biochemistry, 29(42), 9891-9901.
Cosstick R & Williams DM (1987) . Nucleic Acids Res, 15(23), 9921-9932.
Abdelhady R, Senthong P, Eyers CE, Reamtong O, Cowley E, Cannizzaro L, Stimpson J, Cain K, Wilkinson OJ, Williams NH , Barran PE et al () . Chemical Research in Toxicology.
Morton SB, Finger LD, van der Sluijs R, Mulcrone WD, Hodskinson M, Millington CL, Vanhinsbergh C, Patel KJ, Dickman MJ, Knipscheer P , Grasby JA et al () . Journal of the American Chemical Society.

Chapters

Williams DM & Blackburn GM (2022) , Nucleic Acids in Chemistry and Biology (pp. 96-169). The Royal Society of Chemistry
(2007) In Blackburn GM, Gait MJ, Loakes D & Williams DM (Ed.), Nucleic Acids in Chemistry and Biology (pp. vii-viii). Royal Society of Chemistry
(2007) In Blackburn GM, Gait MJ, Loakes D & Williams DM (Ed.) Royal Society of Chemistry
Blackburn GM, Gait MJ, Loakes D & Williams DM (2006) Synthesis of Oligonucleotides, NUCLEIC ACIDS IN CHEMISTRY AND BIOLOGY, THIRD EDITION (pp. 143-166).
Blackburn GM, Gait MJ, Loakes D & Williams DM (2006) RNA Structure and Function, NUCLEIC ACIDS IN CHEMISTRY AND BIOLOGY, THIRD EDITION (pp. 253-293).
Blackburn GM, Gait MJ, Loakes D & Williams DM (2006) Reversible Small Molecule-Nucleic Acid Interactions, NUCLEIC ACIDS IN CHEMISTRY AND BIOLOGY, THIRD EDITION (pp. 341-382).
Blackburn GM, Gait MJ, Loakes D & Williams DM (2006) Protein-Nucleic Acid Interactions, NUCLEIC ACIDS IN CHEMISTRY AND BIOLOGY, THIRD EDITION (pp. 383-425).
Blackburn GM, Gait MJ, Loakes D & Williams DM (2006) Physical and Structural Techniques Applied to Nucleic Acids, NUCLEIC ACIDS IN CHEMISTRY AND BIOLOGY, THIRD EDITION (pp. 427-457).
Blackburn GM, Gait MJ, Loakes D & Williams DM (2006) Nucleosides and Nucleotides, NUCLEIC ACIDS IN CHEMISTRY AND BIOLOGY, THIRD EDITION (pp. 77-142).
Blackburn GM, Gait MJ, Loakes D & Williams DM (2006) Nucleic Acids in Chemistry and Biology 3rd Edition Introduction and Overview, NUCLEIC ACIDS IN CHEMISTRY AND BIOLOGY, THIRD EDITION (pp. 1-12).
Blackburn GM, Gait MJ, Loakes D & Williams DM (2006) Nucleic Acids in Biotechnology, NUCLEIC ACIDS IN CHEMISTRY AND BIOLOGY, THIRD EDITION (pp. 167-207).
Blackburn GM, Gait MJ, Loakes D & Williams DM (2006) Genes and Genomes, NUCLEIC ACIDS IN CHEMISTRY AND BIOLOGY, THIRD EDITION (pp. 209-251).
Blackburn GM, Gait MJ, Loakes D & Williams DM (2006) DNA and RNA Structure, NUCLEIC ACIDS IN CHEMISTRY AND BIOLOGY, THIRD EDITION (pp. 13-75).
Blackburn GM, Gait MJ, Loakes D & Williams DM (2006) Covalent Interactions of Nucleic Acids with Small Molecules and Their Repair, NUCLEIC ACIDS IN CHEMISTRY AND BIOLOGY, THIRD EDITION (pp. 295-339).
Grasby JA & Williams DM () , Organophosphorus Chemistry (pp. 196-264). Royal Society of Chemistry

Conference proceedings papers

Senthong P, Williams DM, Wilkinson O, Millington C, Marriott A, Watson AJ, Kelly JR, Latypov V, McGown G, Thorncroft MR , Eyers CE et al (2012) The Nitrosated Bile Acid DNA Lesion, O-6-carboxymethylguanine, Is a Substrate for Human O-6-alkylguanine DNA Alkyltransferase. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Vol. 53 (pp S36-S36)
Sultana T, Wilkinson OJ, Heath AW, Williams DM & Carlring J (2012) Impact of a novel conjugation method on the efficiency of CD40mAb-antigen conjugate vaccines in vivo. IMMUNOLOGY, Vol. 137 (pp 763-763)
Zhang F, Tsunoda M, Wilkinson O, Millington CL, Williams DM & Takénaka A (2012) . Acta Crystallographica Section A Foundations of Crystallography, Vol. 68(a1) (pp s166-s166)
Zhang F, Jiang J, Suzuki K, Hoque MM, Tsunoda M, Wilkinson O, Millington CL, Williams DM & Takénaka A (2011) . Acta Crystallographica Section A Foundations of Crystallography, Vol. 67(a1) (pp C286-C287)
Haraguchi T, Shimizu S, Ma X, Kurose T, Juan ECM, Sekine M, Shibata T, Williams DM & Takenaka A (2008) . Acta Crystallographica Section A Foundations of Crystallography, Vol. 64(a1) (pp C298-C298)

Teaching interests: Organic Chemistry

Teaching activities

Undergraduate and postgraduate taught modules

Chemistry and the World Around Us (Level 1): Magic Medicines
This course aims to develop an appreciation of some of the types of medicines that are available, how they were discovered and how they work to control diseases.
Aromatic chemistry (Level 2)
This module reviews the concept of aromaticity and the mechanisms of reactions of aromatic systems, particularly benzene and its derivatives.
Introduction to Organic Synthesis 1 (Level 2)
This module revises the reactions of carbonyl compounds with nucleophiles, introduces conjugate addition reactions (electrophilic alkenes), and discusses the acid and base-catalysed reactions of carbonyl compounds at the α-carbon via enols and enolates. Methods for the synthesis of amines are also discussed.
Heterocyclic Chemistry (Level 3)
This lecture course introduces aromatic and non-aromatic heterocyclic compounds.

Support Teaching:

Tutorials: Level 2 Organic Chemistry.

Laboratory Teaching:

Level 2 Organic Laboratories
Level 4 Research Project