Chemistry: Medicinal Chemistry, Organic Chemistry, Biological Chemistry

CHEMISTRY, BIOCHEMISTRY, PHARMACOLOGY, PROTEIN SURFACE MIMETICS, GPCR REGULATION, ENZYME REGULATION, ANTI-INFLAMMATORY RESEARCH, ANTI-INFECTIVES RESEARCH, ANTI-CANCER RESEARCH, NEURODEGENERATIVE RESEARCH, CARDIOVASCULAR RESEARCH



Chemistry researchers in our group develop expertise in medicinal chemistry, organic chemistry and biological chemistry; conducting solution and solid phase organic synthesis; structure determination through 2D NMR spectroscopy; computer-aided molecular and drug design; and study interactions between small molecules, and with proteins, DNA and RNA. We particularly focus on developing general approaches to basic and strategic chemistry that are applicable to diverse classes of chemical structures. We spend a great deal of time controlling molecular shape, intramolecular hydrogen bonding, nucleophilicity/electrophilicity in order to influence chemical reactivity and molecular recognition. Outcomes are new chemical reactions, novel chemical mechanisms, novel organic compounds, new chemical structures; new enzyme inhibitors, protein agonists and antagonists, and small molecule structural mimics of protein surfaces; and new leads to drugs, diagnostics and vaccines. Our group includes a large number of biochemists and pharmacologists who collaborate in studies on those of our compounds that have been designed to have biological activities.

 

Selected Publications (Medicinal, Organic, Biological Chemistry) 

2019:

Crystal structures of protein-bound cyclic peptides. Malde AK, Hill TA, Iyer A, Fairlie DP. Chem Rev 2019, May 2. doi: 10.1021/acs.chemrev.8b00807.

Oxazole-benzenesulfonamide derivatives inhibit HIV-1 reverse transcriptase interaction with cellular eEF1A and reduce viral replication. Rawle DJ, Li D, Wu Z, Wang L, Choong M, Lor M, Reid RC, Fairlie DP, Harris J, Tachedjian G, Poulsen SA, Harrich D. J Virol 2019, 93(12), pii: e00239-19.

Structure-activity relationships of wollamide cyclic hexapeptides with activity against drug-resistant and intracellular mycobacterium tuberculosis. Khalil ZG, Hill TA, De Leon Rodriguez LM, Lohman RJ, Hoang HN, Reiling N, Hillemann D, Brimble MA, Fairlie DP, Blumenthal A, Capon RJ. Antimicrob Agents Chemother 2019, 63(3), pii: e01773-18.


2018:

Chemical Approaches To Modulating Complement-Mediated Diseases. Iyer A, Xu W, Reid RC, Fairlie DP. J Med Chem 201861, 3253-3276.

Bicyclic Helical Peptides as Dual Inhibitors Selective for Bcl2A1 and Mcl-1 Proteins. de Araujo AD, Lim J, Wu KC, Xiang Y, Good AC, Skerlj R, Fairlie DP. J Med Chem 201861, 2962-2972.

Glucuronic acid as a helix-inducing linker in short peptides. Wu C, Hoang HN, Liu L, Fairlie DP. Chemical Communications 2018, 54, 2162-2165. 

Chemically diverse helix-constrained peptides using selenocysteine crosslinking. Dantas de Araujo A, Perry SR, Fairlie DP. Org Lett 2018, 20, 1453-1456. 

Contiguous hydrophobic and charged surface patches in short helix-constrained peptides drive cell permeability. Perry SR, Hill TA, de Araujo AD, Hoang HN, Fairlie DP. Org Biomol Chem 2018, 16, 367-371. 

 

2017:

Stabilising short-lived Schiff base derivatives of 5-aminouracils that activate mucosal-associated invariant T cells. Mak JYW, Xu W, Reid RC, Corbett AJ, Meehan B, Wang H, Chen Z, Rossjohn J, McCluskey J, Liu L*, Fairlie* DP. Nature Commun 20178, 14599.

Exploiting a novel conformational switch to control innate immunity mediated by complement protein C3a. Lohman R-J, Hamidon JK, Reid RC, Rowley JA, Yau M-K, Halili MA, Nielsen DS, Lim J, Wu K-C, Loh Z, Do A, Suen JY, Iyer A, Fairlie DP. Nature Commun 20178, 351.

Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells.  Keller AN, Eckle SBG, Xu W, Liu L, Hughes VA, Mak JYW, Meehan B, Pediongco T, Birkinshaw RW, Chen Z, Wang H, D’Souza C, Kjer-Nielsen L, Gheradin NA, Godfrey DI, Kostenko L, Corbett AJ, Purcell AW, Fairlie DP*, McCluskey J*, Rossjohn J*. Nature Immunol 2017, 18, 402-411. 

Total synthesis of the Mycobacterium tuberculosis dideoxymycobactin-838 and stereoisomers: Diverse CD1a-restricted T cells display a common hierarchy of lipopeptide recognition. Cheng JMH, Liu L, Pellicci DG, Reddiex S, Cotton RN, Cheng T-Y, Young DC, Van Rhijn I, Moody DB, Rossjohn J, Fairlie DP, Godfrey DI, Williams SJ. Chem Eur J 201723, 1694 – 1701.

Stereoelectronic effects on dienophile separation influence the Diels-Alder synthesis of molecular cleftsStoermer MJ, Wickramasinghe WA, Byriel KA, Hockless DCR, Skelton BW, Sobolev AN, White AH, Mak JYW, Fairlie DP. Eur J Org Chem 2017, 6793–6796. 

Biased signaling by agonists of protease activated receptor 2. Jiang Y, Yau M-K, Kok WM, Lim J, Wu K-C, Liu L, Hill TA, Suen JY, Fairlie DP. ACS Chem Biol 2017, 12, 1217-1226. 

Orally Absorbed Cyclic Peptides. Nielsen DS, Shepherd NE, Xu W, Lucke AJ, Stoermer MJ, Fairlie DP. Chem Rev 2017117, 8094–8128.

Electrophilic helical peptides that bind covalently, irreversibly and selectively in a protein-protein interaction site. Dantas de Araujo A, Lim J, Good AC, Skerlj RT, Fairlie DP*. ACS Med Chem Lett 20178, 22−26.

Downsizing Proto-oncogene cFos to Short Helix-Constrained Peptides That Bind Jun. Baxter D, Perry SR, Hill TA, Kok WM, Zaccai NR, Brady RL, Fairlie DP, Mason JM. ACS Chem Biol 2017, 12, 2051-2061. 

Helix-constraints and amino acid substitution in GLP-1 increase cAMP and insulin secretion but not beta arrestin 2 signalling. Plisson F, Hill TA, Mitchell JM, Hoang HN, de Araujo AD, Xu W, Cotterell A, Edmonds DJ, Stanton RV, Derksen DR, Loria PM, Griffith DA, Price DA, Liras S, Fairlie DP*. Eur J Med Chem 2017, 127, 703-714.

Europium-Labeled Synthetic C3a Protein as a Novel Fluorescent Probe for Human Complement C3a Receptor. de Araujo AD, Wu C, Wu K-C, Reid RC, Durek T, Lim J, Fairlie DP. Bioconjugate Chem 2017, 28, 1669-1676.

Quinazolinone derivatives as inhibitors of homologous recombinase RAD51. Ward A, Dong L, Harris JM, Khanna KK, Al-Ejeha F, Fairlie DP, Wiegmans AP, Liu L. Bioorg Med Chem Lett 2017, 27, 3096-3100.

Tolyporphin Macrocycles from the Cyanobacterium Tolypothrix nodosa Selectively Bind Copper and Silver and Reverse Multidrug Resistance. Prinsep MR, Appleton TG, Hanson GR, Lane I, Smith CD, Puddick J, Fairlie DP. Inorg Chem 2017, 56, 5577-5585. 

Alpha helix nucleation by a simple cyclic tetrapeptide. Hoang HN, Wu C, Beyer RL, Hill TA, Fairlie DP. Aust J Chem 2017, 70, 213–219. 


2016:

Helix nucleation by the smallest known alpha helix in water. Hoang HN, Driver RW, Beyer RL, Hill TA, de Araujo AD, Plisson F, Harrison RS, Goedecke L, Shepherd NE, Fairlie DP*. Angew Chem Int Edit 2016, 55, 8275-8279.

PAR2 modulators derived from GB88. Yau MK, Liu L, Suen JY, Lim J, Lohman RJ, Cotterell AJ, Barry GD, Mak JYC, Vesey DA, Reid RC, Fairlie DP*. ACS Med Chem Lett 2016, 7, 1179-1184

Potent Small Agonists Of Protease Activated Receptor 2. Yau MK, Suen JY, Xu W, Lim J, Liu L, Adams MN, He Y, Hooper JD, Reid RC, Fairlie DP*. ACS Med Chem Lett 20167, 105–110.

Downsizing the BAD BH3 peptide to small constrained αlpha helices with improved ligand efficiency. Shepherd NE, Harrison RS, Ruiz-Gomez G, Abbenante G, Mason JM, Fairlie DP*. Org Biomol Chem 201614, 10939-10945. [special issue on cyclic peptides]

Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists. Seow V, Lim J, Cotterell AJ, Yau MK, Xu W, Lohman RJ, Kok WM, Stoermer MJ, Sweet MJ, Reid RC, Suen JY, Fairlie DP*. Science Reports 20166, 24575. doi: 10.1038/srep24575.

Benzylamide antagonists of protease activated receptor 2 with anti-inflammatory activity. Yau MK, Liu L, Lim J, Lohman RJ, Cotterell AJ, Suen JY, Vesey DA, Reid RC, Fairlie DP*. Bioorg Med Chem Lett 201626, 986-991.

Histone Deacetylase Inhibitors Promote Mitochondrial Reactive Oxygen Species Production and Bacterial Clearance by Human Macrophages. Ariffin JK, das Gupta K, Kapetanovic R, Iyer A, Reid RC, Fairlie DP, Sweet MJ. Antimicrob Agents Chemother 2016, 60, 1521-1529.  

Protease activated receptor 2 (PAR2) modulators: a patent review (2010-2015). Yau MK, Lim J, Liu L, Fairlie DP*. Expert Opinion on Therapeutic Patents 201626, 471-483. 

Antagonism of the proinflammatory and pronociceptive actions of canonical and biased agonists of protease-activated receptor-2. Lieu T, Savage E, Zhao P, Edgington-Mitchell L, Barlow N, Bron R, Poole DP, McLean P, Lohman RJ, Fairlie DP, Bunnett NW. Br J Pharmacol2016173, 2752-2765. 

Differential anti-inflammatory activity of low versus high dose HDAC inhibitors in human macrophages and collagen induced arthritis in rats. Lohman RJ, Iyer A, Fairlie TJ, Cotterell A, Gupta P, Reid RC, Vesey DA, Sweet MJ, Fairlie DP*. J Pharmacol Exp Ther 2016356, 387-396.        

Truncated glucagon-like peptide-1 and exendin-4 α-conotoxin pl14a peptide chimeras maintain potency, α-helicity and reveal interactions vital for cAMP signaling in vitro. Swedberg JE, Schroeder CI, Mitchell J, Fairlie DP, Edmonds DJ, Griffith DA, Ruggeri RB, Derksen DR, Loria PM, Price DA, Liras S, Craik DJ. J Biol Chem 2016291, 15778-15787.

Development of cell-penetrating peptide-based drug leads to inhibit MDMX:p53 and MDM2:p53 interactions. Philippe G, Huang YH, Cheneval O, Lawrence N, Zhang Z, Fairlie DP, Craik DJ, de Araujo AD, Henriques ST. Biopolymers 2016, 106, 853-863.

Stapling peptides using cysteine crosslinking. Fairlie DP, de Araujo AD. Biopolymers 2016, 106, 843-852. 

 

2015:

Short hydrophobic peptides with cyclic constraints are potent glucagon-like peptide-1 receptor (GLP-1R) agonists. Hoang HN, Song K, Hill TA, Derksen DR, Edmonds DJ, Kok WM, Limberakis C, Liras S, Loria PM, Mascitti V, Mathiowetz AM, Mitchell JM, Piotrowski DW, Price DA, Stanton RV, Suen JY, Withka JM, Griffith DA, Fairlie DP*. J Med Chem 201558, 4080-4085.

Small molecule inhibitors of disulfide bond formation by the bacterial DsbA-DsbB dual enzyme system. Halili MA, Bachu P, Lindahl F, Bechara C, Mohanty B, Reid RC, Scanlon MJ, Robinson CV, Fairlie DP*, Martin JL*. ACS Chem Biol 201510, 957-964.

Peptide inhibitors of the Escherichia coli DsbA oxidative machinery essential for bacterial virulence. Duprez W, Premkumar L, Halili M, Lindahl F, Reid RC, Fairlie DP*, Martin JL*. J Med Chem 201558, 577-587.

Potent complement C3a receptor agonists derived from oxazole amino acids: Structure-activity relationships. Singh R, Reed AN, Chu P, Scully CC, Yau MK, Suen JY, Durek T, Reid RC, Fairlie DP*. Bioorg Med Chem Lett 201525, 5604-5608.

Helix-constrained nociceptin peptides are potent agonists and antagonists of ORL-1 and nociception. Lohman RJ, Harrison RS, Ruiz-Gomez G, Hoang HN, Shepherd NE, Chow S, Hill TA, Madala PK, Fairlie DP*. Vitamins and Hormones 201597, 1-55. 

Flexibility versus Rigidity for Orally Bioavailable Cyclic Hexapeptides. Nielsen DS, Lohman RJ, Hoang HN, Hill TA, Jones A, Lucke AJ, Fairlie DP*. Chembiochem 201516, 2289-2293. 

Recognition of Vitamin B precursors and byproducts by Mucosal Associated Invariant T cells. Eckle SB, Corbett AJ, Keller A, Chen Z, Godfrey DI, Liu L, Mak JY, Fairlie DP*, Rossjohn J*, McCluskey J*. J Biol Chem 2015, 290, 30204-30211.

Toward peptide-based inhibitors as therapies for Parkinson's disease. Mason JM, Fairlie DP. Future Med Chem 20157, 2103-2105.

Cyclic alpha-conotoxin peptidomimetic chimeras as potent GLP-1R agonists. Swedberg JE, Schroeder CI, Mitchell JM, Durek T, Fairlie DP, Edmonds DJ, Griffith DA, Ruggeri RB, Derksen DR, Loria PM, Liras S, Price DA, Craik DJ. Eur J Med Chem 2015103, 175-184. 

Comparing Sixteen Scoring Functions for Predicting Biological Activities of Ligands for Protein Targets. Xu W, Lucke AJ, Fairlie DP*. J Mol Graphics Modelling 201557, 76-88.

Three Homology Models of PAR2 Derived from Different Templates: Applications to Antagonist Discovery. Perry SR, Xu W, Wirija A, Lim J, Yau MK, Stoermer MJ, Lucke AJ, Fairlie DP*. J Chem Inf Model 201555, 1181-1191.

Repurposing Registered Drugs as Antagonists for Protease-Activated Receptor 2. Xu W, Lim J, Goh CY, Suen JY, Jiang Y, Yau MK, Wu KC, Liu L, Fairlie DP*. J Chem Inf Model 201555, 2079-2084.

Virtual Screening of Peptide and Peptidomimetic Fragments Targeted to Inhibit Bacterial Dithiol Oxidase DsbA. Duprez W, Bachu P, Stoermer MJ, Tay S, McMahon RM, Fairlie DP*, Martin JL*. PLoS One 201510(7): e0133805.

Profiling the anti-protozoal activity of anti-cancer HDAC inhibitors against Plasmodium and Trypanosoma parasites. Engel JA, Jones AJ, Avery VM, Sumanadasa SD, Ng SS, Fairlie DP, Adams TS, Andrews KT. Int J Parasitol Drugs Drug Resist 20155, 117-126.

 

2014:

Stereoelectronic effects dictate molecular conformation and biological function of heterocyclic amides. Reid RC, Yau MK, Singh R, Lim J, Fairlie DP*. J Am Chem Soc 2014, 136, 11914-11917. Recommended by Faculty1000Prime.

Potent Heterocyclic Ligands for Human Complement C3a Receptor Reid RC, Yau M-K, Singh R, Hamidon JK, Lim J, Stoermer MJ, Fairlie DP*. J Med Chem 2014, 57, 8459-8470.

Improving on Nature: Making a Cyclic Heptapeptide Orally Bioavailable. Nielsen DS, Hoang HN, Lohman RJ, Hill TA, Lucke AJ, Craik DJ, Edmonds DJ, Griffith DA, Rotter CJ, Ruggeri RB, Price DA, Liras S, Fairlie DP*. Angew Chem Int Edit 2014, 53, 12059-12063.

Constraining Cyclic Peptides To Mimic Protein Structure Motifs. Hill TA, Shepherd NE, Diness F, Fairlie DP*. Angew Chem Int Edit 2014, 53, 13020-13041. 

Comparative Alpha Helicity of Cyclic Pentapeptides in Water. de Araujo AD, Hoang HN, Kok WM, Diness F, Gupta G, Hill TA, Driver RW, Price DA, Liras S, Fairlie DP*. Angew Chem Int Edit 2014, 53, 6965-6999.

T cell activation by transitory neo-antigens derived from distinct microbial pathways. Corbett AJ, Eckle SBG, Birkinshaw RW, Liu L, Patel O, Mahony J, Chen Z, Reantra-goon R, Meehan B, Cao H, Williamson NA, Strugnell RA, Sinderen DV, Mak JYW, Fairlie DP*, Lars Kjer-Nielsen*, Rossjohn J*, McCluskey J*. Nature, 2014, 509(7500), 361-365. ISI Highly Cited.

Helical cyclic pentapeptides constrain HIV-1 Rev peptide for enhanced RNA binding. Harrison RS, Shepherd NE, Hoang HN, Beyer RL, Ruiz-Gómez G, Kelso MJ, WM Kok, TA Hill, Abbenante G, Fairlie DP*. Tetrahedron 2014, 70, 7645-7650 [special issue on cyclic peptides].

Cyclic Penta- and Hexa- Leucine Peptides Without N-Methylation Are Orally AbsorbedHill TA, Lohman RJ, Hoang HN, Nielsen DS, Scully CCG, Kok WM, Liu L, Lucke AJ, Stoermer MJ, Schroeder CI, Chaousis S, Colless B, Bernhardt PV, Edmonds DJ, Griffith DA, Rotter CJ, Ruggeri RB, Price DA, Liras S, Craik DJ, Fairlie DP*. ACS Med Chem Lett 2014, 5, 1148-1151. Faculty1000Prime Recommendation. 

Lysine acetylation in sexual stage malaria parasites is a target for antimalarial small molecules. Trenholme K, Marek L, Duffy S, Pradel G, Fisher G, Hansen FK, Skinner-Adams TS, Butterworth A, Julius Ngwa C, Moecking J, Goodman CD, McFadden GI, Sumanadasa SD, Fairlie DP, Avery VM, Kurz T, Andrews KT. Antimicrob Agents Chemother 2014, 58, 3666-3678.

Rational design and synthesis of an orally bioavailable peptide guided by NMR amide temperature coefficients. Wang CK, Northfield SE, Colless B, Chaousis S, Hamernig I, Lohman RJ, Nielsen DS, Schroeder CI, Liras S, Price DA, Fairlie DP*, Craik DJ*. Proc Natl Acad Sci U S A. 2014111, 17504-17509.

Crystal Structure of the Dithiol Oxidase DsbA Enzyme from Proteus Mirabilis Bound Non-Covalently to an Active Site Peptide Ligand. Kurth F, Duprez W, Premkumar L, Schembri M, Fairlie DP*, Martin JL*. J Biol Chem 2014, 289, 19810-19822.

 

2013:

Downsizing a Human Inflammatory Protein to a Small Molecule with Equal Potency and Functionality. Reid RC, Yau M-K, Singh R, Hamidon JK, Reed AN, Chu P, Suen JY, Stoermer MJ, Blakeney JS, Lim J, Faber JM, Fairlie DP. Nature Communications 2013, 42802. doi: 10.1038/ncomms3802.

Towards Drugs for Protease-Activated Receptor 2 (PAR2). Yau MK, Liu L, Fairlie DP. J Med Chem 201356, 7477–7497.

Efficient chemical synthesis of human complement protein C3a. Ghassemian A, Wang CI, Yau MK, Reid RC, Lewis RJ, Fairlie DP, Alewood PF, Durek T. Chem Commun 201349, 2356-2358.

Recognition of vitamin B metabolites by mucosal-associated invariant T cells. Patel O, Kjer-Nielsen L, Nours JL, Eckle SBG, Bikinshaw R, Beddoe T, Corbett AJ, Liu L, Miles JJ, Mehan B, Reantragoon R, Sandoval-Romero ML, Sullivan LC, Brooks AG, Chen Z, Fairlie DP, McCluskey J, Rossjohn J. Nature Communications 20134, 2142 doi: 10.1038/ncomms3142. 

The Future of Peptide-based Drugs. Craik DJ, Fairlie DP, Liras S, Price D. Chem Biol Drug Des, 2013, 81, 136-147. ISI Highly Cited. ISI Hot Paper. [>100 citations] 

Truncated and helix-constrained peptides with high affinity and specificity for the cFos coiled-coil of AP-1. Rao T, Ruiz-Gómez G, Hill TA, Hoang HN, Fairlie DP, Mason JM. PLoS One 2013, 8(3), e59415.

 

2012:

Catalyst-Free N-arylation Using Unactivated Fluorobenzenes. Diness F, Fairlie DP. Angew. Chem. Int. Edit. 201251, 8012-8016.

MR1 presents microbial vitamin B metabolites to MAIT cells. Kjer-Nielsen L, Patel O, Nours JL, Meehan B, Corbett AJ, Liu L, Bhati M, Chen Z, Kostenko L, Reantragoon R, Williamson NA, Purcell AW, Dudek NL, McConville MJ, O’Hair RAJ, Khairallah GN, Godfrey DI, Fairlie DP, Rossjohn J, McCluskey J. Nature 2012, 491, 717-723. ISI Highly Cited. ISI Hot Paper.[>100 citations] 

Total Synthesis, Structure, and Oral Absorption of a Thiazole Cyclic Peptide, Sanguinamide A. Nielsen DS, Hoang HN, Lohman RJ, Diness F, Fairlie DP. Org Lett. 2012, 14, 5720–5723.

Folding pentapeptides into left and right handed alpha helices. Hoang, HN, Abbenante G, Hill TA, Ruiz-Gomez G, Fairlie DP. Tetrahedron, 201268, 4513–4516 [special issue on foldamers].

 

2011:

Protein Alpha Turns Recreated in Structurally Stable Small Molecules. Hoang HN, Driver RW, Beyer RL, Malde AK, Le GT, Abbenante G, Mark AE, Fairlie DP. Angew. Chem. Int. Ed. Engl. 2011, 50, 11107-11111. 

VIP: Amyloid Formation from an α-Helix Peptide Bundle Is Seeded by 310-Helix Aggregates. Singh Y, Sharpe PC, Hoang HN, Lucke AJ, McDowall AW, Bottomley SP, Fairlie DP. Chem. Eur. J.  2011, 17, 151-160. 

Synthesis of the Thiazole-Thiazoline Fragment of Largazole Analogues. Diness F, Nielsen DS, Fairlie DP. J. Org. Chem. 2011, 76, 9845-9851. 

Ex Vivo Activity of Histone Deacetylase Inhibitors against Multidrug-Resistant Clinical Isolates of Plasmodium falciparum and P. vivax. Marfurt J, Chalfein F, Prayoga P, Wabiser F, Kenangalem E, Piera KA, Fairlie DP, Tjitra E, Anstey NM, Andrews KT, Price RN. Antimicrob. Agents Chemother. 2011, 55, 961-966. 

 

2010:

Downsizing human, bacterial, and viral proteins to short water-stable alpha helices that maintain biological potency. Harrison RS, Shepherd NE, Hoang HN, Ruiz-Gómez G, Hill TA, Driver RW, Desai VS, Young PR, Abbenante G, Fairlie DP. Proc Natl Acad Sci U S A. 2010, 107, 11686-11691. 

Novel agonists and antagonists for human protease activated receptor 2. Barry GD, Suen JY, Le GT, Cotterell A, Reid RC, Fairlie DP. J. Med. Chem. 2010, 53, 7428-7440. 

Novel Helix-Constrained Nociceptin Derivatives Are Potent Agonists and Antagonists of ERK Phosphorylation and Thermal Analgesia in Mice. Harrison RS, Ruiz-Gómez G, Hill TA, Chow SY, Shepherd NE, Lohman RJ, Abbenante G, Hoang HN, Fairlie DP. J. Med. Chem. 2010, 53, 8400–8408. 

Non-covalent tripeptidylbenzyl and cyclohexyl amine inhibitors of the cysteine protease caspase-1. Löser R, Abbenante G, Madala PK, Halili M, Le GT, Fairlie DP. J. Med. Chem. 2010, 53, 2651-2655. 

Selective hexapeptide agonists and antagonists for human complement C3a receptor. Scully CC, Blakeney JS, Singh R, Hoang HN, Abbenante G, Reid RC, Fairlie DP. J. Med. Chem. 201053, 4938-4948. 

Update 1 of: Over One Hundred Peptide-Activated G Protein-Coupled Receptors Recognize Ligands with Turn Structure. Gloria Ruiz-Gmez, Joel D. A. Tyndall, Bernhard Pfeiffer, Giovanni Abbenante and David P. Fairlie. Chemical Reviews, 2010, 110(4), PR1-PR41.

Update 1 of: Proteases Universally Recognize Beta Strands in their active sites. Madala PK, Tyndall JD, Nall T, Fairlie DP. Chemical Reviews 2010, 110(6), PR1-PR31.

Update 1 of: Beta-Strand Mimetics. Loughlin WA, Tyndall JD, Glenn MP, Hill TA, Fairlie DP. Chemical Reviews 2010, 110(6), PR32-PR69.

Inhibitors Selective For HDAC6 In Enzymes and Cells. Gupta PK, Reid RC, Liu L, Lucke AJ, Broomfield SA, Andrews MR, Sweet MJ, Fairlie DP. Bioorg. Med. Chem. Lett. 2010, 20, 7067-7070. 

Antimalarial Histone Deacetylase Inhibitors Containing Cinnamate or NSAID Components. Wheatley NC, Andrews KT, Tran TL, Lucke AJ, Reid RC, Fairlie DP. Bioorg. Med. Chem. Lett. 2010, 20, 7080-7084.

 

2009:

Left- and Right-Handed Alpha-Helical Turns in Homo- and Hetero-Chiral Helical Scaffolds. Shepherd NE, Hoang HN, Abbenante G, Fairlie DP. J Am Chem Soc. 2009, 131, 15877-15886. 

Ma MT, Hoang HN, Scully CCG, Appleton TG, Fairlie DP Metal Clips That Induce Unstructured Pentapeptides To Be Alpha Helical In Water J Am Chem Soc 2009, 131, 4505-4512. 

Structure activity relationships for substrate based inhibitors of human complement factor B. Ruiz-Gómez, G.; Lim, J.; Halili, MA; Le, GT; Madala, PK; Abbenante G.; Fairlie DP J Med Chem 2009, 52, 6042-6052. 

Complement Factor C2, Inhibiting A Latent Serine Protease In The Classical Pathway Of Complement Activation. Halili MA, Ruiz-Gómez G, Le GT, Abbenante G, Fairlie DP. Biochemistry 2009, 48, 8466–8472. 

A cyclic beta-strand tripeptide with an alpha-helix like CD spectrum. Driver R. W.; Hoang, H. N.; Abbebante, G, Fairlie, D. P. Org. Lett. 2009, 11, 3092–3095.  

 

Some examples of earlier publications:

Potent cationic inhibitors of West Nile virus NS2B/NS3 protease with serum stability, cell permeability and antiviral activity.Stoermer MJ, Chappell KJ, Liebscher S, Jensen CM, Gan CH, Gupta PK, Xu WJ, Young PR, Fairlie DP. J Med Chem. 2008, 51, 5714-1521. 

Cyclooligomerization of a Helix-Bearing Template into Macrocycles Bearing Multiple Helices. Beyer RL, Singh Y, Fairlie DP. Org. Lett. 2008, 10, 3481-3484.                                                  

Reid, R. C.; Fairlie, D. P. Parallel Synthesis Of Anticancer, Antiinflammatory and Antiviral Agents Derived From L- and D- Amino Acids in "High-Throughput Lead Optimisation In Drug Discovery", Ed. Tushar Kshirsagar; CRC Press, Taylor and Francis, New York; ISBN: 9780849372681, Chapter 7, 2008, 177-194. 

Crystal Structures of Highly Constrained Substrate and Hydrolysis Products Bound to HIV-1 Protease. Implications for Catalytic Mechanism. Tyndall, J. D. A.; Pattenden, L. K.; Reid, R. C.; Hu, S.-H.; Alewood, D.; Alewood, P. F.; Walsh, T.; Fairlie, D. P.; Martin, J. L. Biochemistry 2008, 47, 3736-44.

Andrews, K.T.; Tran, T.N.; Lucke, A.J.; Kahnberg, P.; Le, G.T.; Boyle, G.M.; Gardiner, D.L.; Skinner-Adams, T. S.; Fairlie, D.P. Potent new antimalarial agents that cause histone hyperacetylation in Plasmodium falciparum. Antimicrobial Antiinfectives Chemother. 2008, 52, 1454-1461.

Nonpeptidic ligands for peptide-activated G protein-coupled receptors. Blakeney JS, Reid RC, Le GT, Fairlie DP. Chemical Reviews 2007, 107, 2960-3041. 

Profiling the enzymatic properties and inhibition of human complement factor B. Le, G.T.; Abbenante, G.; Fairlie, D.P. J. Biol. Chem. 2007, 282, 34809-34816. 

A new paradigm for protein kinase inhibition : Blocking phosphorylation without targeting ATP binding. Bogoyevitch, M.A.; Fairlie, D.P. Drug Discovery Today 2007, 12, 622-633. [>100 citations]   

Unexpected Photolytic Decomposition of Alkyl Azides Under Mild Conditions. Abbenante, G.; Le, G. T.; Fairlie, D.P. J. Chem. Soc. Chem Commun. 2007, 43, 4501-4503.   

Organic azide inhibitors of cysteine proteases. Le, G.T.; Abbenante,G.; Madala, P.K.; Hoang, H.N.; Fairlie, D.P. J. Am. Chem. Soc. 2006, 128, 12396-12397.

Modular Alpha Helical Mimetics With Antiviral Activity Against Respiratory Syncitial Virus. Shepherd, N. E.; Hoang, H. N.; Desai, V. S.; Letouze, E.; Young, P. R.; Fairlie D. P.  J. Am. Chem. Soc. 2006, 128, 13284-13289.

Design, Synthesis, Potency and Cytoselectivity Of Anticancer Agents Derived By Parallel Synthesis From alpha-Aminosuberic Acid. Kahnberg, P.; Lucke, A.J.; Glenn, M.P.; Boyle, G.M.; Tyndall, J.D.A.; Parsons, P.G.; Fairlie, D. P. J. Med. Chem. 2006, 49, 7611-7622. 

Insights to Substrate Binding and Processing by West Nile Virus NS3 Protease :through Combined Modelling, Protease Mutagenesis, and Kinetic Studies. Chappell, K. J.; Stoermer, M. J.; Fairlie, D. P.; Young, P.R. J. Biol. Chem. 2006, 281, 38448-58. 

Proteases Universally Recognize Beta Strands In Their Active Sites. Tyndall, J. D. A.; Nall, T.; Fairlie, D. P. Chem. Reviews  2005, 105, 973-1000. [>100 citations]  ISI Highly Cited. 

Over 100 Peptide-Activated G Protein-Coupled Receptors Recognize Ligands with Turn Structure. Tyndall, J. D. A.; Pfeiffer, B.; Abbenante,G.; Fairlie, D. P. Chemical Reviews 2005, 105, 793-826. [>100 citations]                

Single Turn Alpha Helical Peptides With Exceptional Stability In Water. Shepherd, N. E.; Hoang, H. N.; Abbenante, G.; Fairlie, D. P.  J. Am. Chem. Soc. 2005, 127, 2974-2983. 

Structural Mimicry of Two Cytochrome b562 Interhelical Loops Using Macrocycles Constrained By Oxazoles and Thiazoles. Singh, Y.; Stoermer, M. J.; Lucke, A.; Guthrie, T.; Fairlie, D. P.  J. Am. Chem. Soc. 2005, 127, 6563-72.  

Site-directed Mutagenesis and Kinetic Studies of the West Nile Virus NS3 Protease Identify Key Enzyme-Substrate Interactions. Chappell,  K. J.; Nall, T.; Stoermer, M.J.; Fang, N.-X.; Tyndall, J.D.A.; Fairlie, D.P.; Young, P.Y. J. Biol. Chem. 2005, 280, 2896-2903.

Site-directed Mutagenesis and Kinetic Studies of the West Nile Virus NS3 Protease Identify Key Enzyme-Substrate Interactions. Chappell,  K. J.; Nall, T.; Stoermer, M.J.; Fang, N.-X.; Tyndall, J.D.A.; Fairlie, D.P.; Young, P.Y. J. Biol. Chem. 2005, 280, 2896-2903.

Comparative Agonist/Antagonist Responses in Mutant Human C5a Receptors Define the Ligand Binding Site. Higginbottom, A.; Cain, S. A.; Woodruff, T. M.; Proctor, L. M.; Madala, P. K.; Tyndall, J. D. A.; Taylor, S. M.; Fairlie, D.P.; Monk, P. N. J. Biol. Chem. 2005, 280 17831-17840.

Protease Inhibitors in the Clinic. Abbenante, G.; Fairlie, D. P. Medicinal Chemistry 2005, 1, 71-104. [>100 citations]   

Beta Strand Mimetics. Loughlin, W. A.; Tyndall, J. D. A.; Glenn, M. P.; Fairlie, D. P. Chem. Reviews 2004, 104, 6085-6117. [>100 citations]  

Alpha-Turn Mimetics: Short Peptide Alpha-Helices Composed Of Cyclic Metallopentapeptide Modules. Kelso, M.J.; Beyer, R. L.; Hoang, H. N.; Lakdawala, A. S.; Snyder, J. P.; Oliver, W. P.; Robertson,  T. A.; Appleton,  T. G.; Fairlie, D. P. J. Am. Chem. Soc. 2004, 126, 4828-4842.

Metal Clips Induce Folding of a Short Unstructured Peptide into an Alpha Helix via Turn Conformations in Water. Kinetic versus Thermodynamic Products. Beyer, R. L.; Hoang, H. N.; Appleton,  T. G.; Fairlie, D. P. J. Am. Chem. Soc. 2004, 126, 15096-15105.  

Consecutive Cyclic Pentapeptide Modules Form Short Alpha-Helices that are Very Stable to Water and Denaturants. Shepherd, N. E.; Abbenante, G.; Fairlie, D. P. Angew Chem. Int. Edit. 2004, 43, 2687-2690. 

Anti-Proliferative And Phenotype-Transforming Antitumor Agents  Derived From Cysteine Glen, M. P.; Kahnberg, P.; Boyle, G. M.; Hansford, K. A.; Hans, D.; Martyn, A. C.; Parsons, G. P.; Fairlie, D. P. J. Med. Chem. 2004, 47, 2984-2994.          

Countering cooperative effects in protease inhibitors using constrained beta strand-mimicking templates in focussed combinatorial libraries. Reid, R. C.; Pattenden, L. K.; Tyndall, J. D. A.; Martin, J. L.; Walsh, T.; Fairlie, D. P. J. Med. Chem. 2004, 47, 1641-51. 

Conformationally Homogeneous Cyclic Tetrapeptides: Useful Three Dimensional Scaffolds. Glenn, M. P.; Kelso, M. J.; Tyndall, J. D. A.; Fairlie, D. P. J. Am. Chem. Soc. 2003, 125, 640-641.            

A Cyclic Metallopeptide That Induces Alpha Helicity In Short Peptide Fragments of Thermolysin. Kelso, M. J.; Hoang, H. N.; Oliver, W. N.; Sokolenko, N.; March, D. R.; Appleton, T. G.; Fairlie, D. P.  Angew Chem. Int. Edit. 200342, 421-424.        

A Convergent Solution Phase Synthesis of the Macrocycle, Ac-Phe-[Orn-Pro-D-Cha-Trp-Arg], a Potent New Anti-Inflammatory Drug. Reid, R. C.; Abbenante, G.; Taylor, S. M.; Fairlie, D. P. J. Org. Chem. 2003, 68, 4464-4471.  

D-Tyrosine As A Chiral Precursor To Potent Inhibitors Of Human Non-Pancreatic Secretory Phospholipase A2 (IIa) With Anti-Inflammatory Activity. Hansford, K. A.; Reid, R. C.; Clark, C. I.; Tyndall, J. D. A.; Whitehouse, M. W.; Guthrie, T.; McGeary, R. P.; Schafer, K.; Martin, J. L.; Fairlie D. P. ChemBioChem. 2003, 4, 181-185. 

Conformationally Constrained Macrocycles That Mimic Tripeptide Beta-Strands In Water and Aprotic Solvents. Reid, R. C.; Kelso, M. J.; Scanlon, M. J.; Fairlie, D. P. J. Am. Chem. Soc. 2002, 124, 5673-5683. 

Beta strand mimicking macrocyclic amino acids. Templates for protease inhibitors with antiviral activity. Glenn, M. P.; Pattenden, L. K.; Reid, R. C.; Tyssen, D. P.; Tyndall, J. D. A.; Birch, C. J.; Fairlie, D. P. J. Med. Chem. 2002, 45, 371-381. 

Regioselective Synthesis of Two Antiparallel Loops on a Macrocyclic Scaffold Constrained by Oxazoles and Thiazoles. Singh, Y.; Stoermer, M. J.; Lucke, A. J.; Glenn, M. P.; Fairlie, D. P. Organic Letters 2002, 4, 3367-70. 

Novel Conical, Cylindrical, and Macrocyclic Peptides From The Cyclooligomerization Of Thiazole Amino Acids. Singh, Y.; Sokolenko, N.; Kelso, M. J.; Gahan, L. C.; Abbenante, G.; Fairlie, D. P. J. Am. Chem. Soc. 2001, 123, 333-334. 

Activity Of Recombinant Dengue 2 Virus NS3 Protease In The Presence Of NS2B Cofactor, Small Peptide Substrates, And Inhibitors. Leung, D.; Schroder, K.; White, H.; Fang, N.-X.; Stoermer, M. J.; Abbenante, G.; Martin, J. L.; Young, P.; Fairlie, D. P. J. Biol. Chem. 2001, 276, 45762-45771. [>100 citations]   

The First Solution Stucture Of A Single Alpha Helical Turn. A Pentapeptide a-Helix Stabilised By A Metal Clip. Kelso, M. J.; Hoang, H. N.; Appleton, T. G.; Fairlie, D. P. J. Am. Chem. Soc. 2000, 122, 10488-10489. 

Is oxidative damage by beta amyloid and prion peptides mediated by hydrogen atom transfer from glycine alpha-carbon to methionine sulfur within beta-sheets? Rauk, A.; Armstrong, D. A.; Fairlie, D. P. J. Am. Chem. Soc. 2000, 122, 9761-9767. 

Protease Inhibitors: Current Status and Future Prospects. Leung D, Abbenante G, Fairlie DP. J. Med. Chem2000, 43, 305-341. [>900 citations] ISI Highly Cited.  

Conformational Selection Of Inhibitors and Substrates By Proteolytic Enzymes : Implications for Drug Design and Polypeptide Processing. Fairlie, D. P.; Tyndall, J. D. A.; Reid, R. C.; Wong, A. K.; Abbenante, G.; Scanlon, M. J.; March, D. R.; Bergman, D. A.;  Chai, C. L. L.; Burkett, B. A. J. Med. Chem. 2000, 43, 1271-1281. [>100 citations]   

Synthesis, Stability, Antiviral Activity, and Protease-Bound Structures of Substrate-Mimicking Constrained Macrocyclic Inhibitors of HIV-1 Protease. Tyndall, J. D. A.; Reid, R. C.; Tyssen, D. P.; Jardine, D. K.; Todd, B.; Passmore , M.; March, D. R.; Pattenden, L. K.; Bergman, D. A.; Alewood, D.; Hu, S-H.; Alewood, P. F.; Birch, C. J.; Martin, J. L.; Fairlie, D. P.  J. Med. Chem. 2000, 43, 3495-3504. 

Characterization of Copper Interactions with Alzheimer Aß Peptides- Identification of an Attomolar Affinity Copper Binding Site on Aß1-42. Atwood, C.S., Scarpa, R.C., Huang, X., Moir, R.D., Jones, W.D., Fairlie, D.P., Tanzi, R.E. and Bush, A.I. J. Neurochem. 2000, 75, 1219-1233. [>100 citations]   

Cyclooligomerisation of Thiazole-Containing Tetrapeptides. Symmetrical Macrocycles with up to 76 Amino Acids. Sokolenko, N.; Abbenante, G.; Scanlon, M. J.; Jones, A.; Gahan, L. R.; Hanson, G. R.; Fairlie, D. P. J. Am. Chem. Soc. 1999, 121, 2603-2604.

Cu(II) potentiation of Alzheimer Aß neurotoxicity: correlation with cell-free hydrogen peroxide production and metal reduction. Huang, X.; Cuajungco, M. P.; Atwood, C. S.; Hartshorn, M. A.; Tyndall, J. D. A.; Hanson, G. R.; Stokes, K. C.; Leopold, M.; Multhaup, G.; Goldstein, L. E.; Scarpa, R. C.; Saunders, A. J.; Lim, J.; Moir, R. D.; Glabe, C.; Bowden, E. F.; Masters, C. L.; Fairlie, D. P.; Tanzi, R. E.; Bush, A. I.