A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing. M. M. Karunakaran, H. Subramanian, Y. Jin, F. Mohammed, B. Kimmel, C. Juraske, L. Starick, A. Nöhren, N. Länder, C. R. Willcox, R. Singh, W. W. Schamel, V. O. Nikolaev, V. Kunzmann, A. J. Wiemer, B. E. Willcox, T. Herrmann. Nat Commun. 14(1):7617. 2023. PubMed

Diester Prodrugs of a Phosphonate Butyrophilin Ligand Display Improved Cell Potency, Plasma Stability, and Payload Internalization. U. Singh, G. Pawge, S. Rani, C. H. Hsiao, A. J Wiemer, D. F. Wiemer. J Med Chem. 66(22):15309-15325. 2023. PubMed

Mutations to the BTN2A1 Linker Region Impact Its Homodimerization and Its Cytoplasmic Interaction with Phospho-Antigen-Bound BTN3A1. K. Nguyen, Y. Jin, M. Howell, C. H. Hsiao, A. J. Wiemer, O. Vinogradova. J Immunol. 211(1):23-33. 2023. PubMed


New Technologies Bloom Together for Bettering Cancer Drug Conjugates. Y. Jin, S. Edalatian Zakeri, R. Bahal, A. J. Wiemer. Pharmacol Rev.  74(3):680-711. 2022. PubMed

Graphical abstract from Jin 2022

Ligand-induced interactions between butyrophilin 2A1 and 3A1 internal domains in the HMBPP receptor complex. C.H. Hsiao, K. Nguyen, Y. Jin, O. Vinogradova and A. J. Wiemer. Cell Chem Biol. 2022. PubMed

Graphical abstract of Hsiao 2022

Stepping Forward in Antibody-drug Conjugate Development. Y. Jin, M. A. Schladetsch, X. Huang, M. J. Balunas, A. J. Wiemer. Pharm Ther. 107917. 2022. PubMed

Synthesis and metabolism of BTN3A1 ligands: studies on diene modifications to the phosphoantigen scaffold. N. M. Harmon, M. M. Poe, X. Huang, R. Singh, B. J. Foust, C. H. Hsiao, D. F. Wiemer, and A. J. Wiemer.  ACS Med Chem Lett. 13:164-170. 2022. PubMed

Efficiency of bis-amidate phosphonate prodrugs. N. A. Lentini, X. Huang, M. A. Schladetsch, C. H. Hsiao, D. F. Wiemer, A. J. Wiemer.  Bioorg Med Chem Lett. 2022. PubMed


Generation of single-chain variable fragment (scFv) libraries for use in phage display. M. A. Schladetsch and A. J. Wiemer. Cur Prot Chem Biol. 2021. PubMed

Incorporation of a FRET Pair within a Phosphonate Diester. N. M. Harmon, X. Huang, C. H. Hsiao, A. J. Wiemer, D. F. Wiemer. Bioorg Chem. 114:105048. 2021. PubMed


Synthesis and Metabolism of BTN3A1 Ligands: Studies on Modifications of the Allylic Alcohol. N. A. Lentini, C. M. Schroeder, N. M. Harmon, X. Huang, M. A. Schladetsch, B. J. Foust, M. M. Poe, C. H. Hsiao, A. J. Wiemer, D. F. Wiemer.  ACS Med Chem Lett. 2020. PubMed

Potent Double Prodrug forms of Synthetic Phosphoantigens. N. M. Harmon, X. Huang, M. A. Schladetsch, C. H. Hsiao, A. J. Wiemer, D. F. Wiemer. Bioorg Med Chem. 2020. 28:115666. PubMed

Metabolic efficacy of phosphate prodrugs and the remdesivir paradigm. A. J. Wiemer. ACS Pharmacol Transl Sci. 2020. 3:613-626. PubMed

Graphical abstract of Wiemer 2020

Structure-Activity Relationships of Butyrophilin 3 Ligands. A. J. Wiemer. ChemMedChem. 2020. 15:1030-1039. PubMed


A luciferase lysis assay reveals in vivo malignant cell sensitization by phosphoantigen prodrugs. J. Li, N. A. Lentini, D. F. Wiemer, A. J. Wiemer. Biochem Pharmacol. 2019. 170:113668. PubMed

Graphical abstract of Li 2019

Stability and Efficiency of Mixed Aryl Phosphonate Prodrugs. B.J. Foust, J. Li, C. H. Hsiao, D. F. Wiemer, A. J. Wiemer. ChemMedChem. 2019. 14(17):1597-1603. PubMed

The paper by Foust was featured on the cover

Regulation of the Notch-ATM-abl axis by geranylgeranyl diphosphate synthase inhibition. S. S. Agabiti, J. Li, W. Dong, M. M. Poe, A. J. Wiemer. Cell Death Dis. 2019. 10(10):733. PubMed

Toward Broad Spectrum DHFR inhibitors Targeting Trimethoprim Resistant Enzymes Identified in Clinical Isolates of Methicillin-Resistant Staphylococcus aureus. S. M. Reeve, D. Si, J. Krucinska, Y. Yan, K. Viswanathan, S. Wang, G. T. Holt, M. S. Frenkel, A. Ojewole, A. Estrada, S. S. Agabiti, J. B. Alverson, N. D. Gibson, N. D. Priestly, A. J. Wiemer, B. R. Donald, D. L. Wright. ACS Infect Dis. 2019. 5(11):1896-1906. PubMed

Synthesis and Bioactivity of the Alanyl Phosphonamidate Stereoisomers Derived from a Butyrophilin Ligand.
N.A Lentini, C.H. Hsiao, G.B. Crull, A.J. Wiemer, D.F. Wiemer. ACS Med Chem Lett. 2019. 10(9):1284-1289.

Probing the Ligand-Binding Pocket of BTN3A1. M. M. Poe, S. S. Agabiti, C. Liu, V. Li, K. A. Teske, C. H. Hsiao, A. J. Wiemer. J Med Chem. 2019. 62(14):6814-6823.PubMed

Graphical abstract of Poe 2019

Tropolone-induced effects on the unfolded protein response pathway and apoptosis in multiple myeloma cells are dependent on iron. S. L. Haney, M. L. Varney, H.R. Safranek, Y.S. Chhonker, N. G-Dayanandan, G. Talmon, D. J. Murry, A. J. Wiemer, D. L. Wright, S. A. Holstein. Leuk Res. 2019. 77:17-27.PubMed


A power law function describes the time- and dose-dependency of Vγ9Vδ2 T cell activation by phosphoantigens. C. H. Hsiao and A. J. Wiemer. Biochem Pharmacol 2018. 158:298-304. PubMed

Graphical abstract of Hsiao 2018

Phosphonamidate prodrugs of a butyrophilin ligand display plasma stability and potent Vγ9Vδ2 T cell stimulation. N. A. Lentini, B. J. Foust, C. H. Hsiao, A. J. Wiemer, D. F. Wiemer. J Med Chem. 2018. 61(19): 8658-8669. PubMed


Mixed aryl phosphonate prodrugs of a butyrophilin ligand. B. J. Foust, M. M. Poe, N. A. Lentini, C. H. Hsiao, A. J. Wiemer, D. F. Wiemer. ACS Med Chem Lett. 2017. 8(9): 914-918. PubMed

Novel tropolones induce the unfolded protein response pathway and apoptosis in multiple myeloma cells. S. L. Haney, C. Allen, M. L. Varney, K. M. Dykstra, E. R. Falcone, S. H. Colligan, Q. Hu, A. M. Aldridge, D. L. Wright, A. J. Wiemer, S. A. Holstein. Oncotarget. 2017. 8(44): 76085-76098. PubMed

The butyrophilin 3A1 intracellular domain undergoes a conformational change involving the juxtamembrane region. K. Nguyen, J. Li, R. Puthenveetil, X. Lin, M. M. Poe, C. H. Hsiao, O. Vinogradova, and A. J. Wiemer. FASEB Journal. 2017. 31(11): 4697-4706. PubMed

Geranylgeranyl diphosphate synthase inhibition induces apoptosis that is dependent upon GGPP depletion, ERK phosphorylation and caspase activation. S. S. Agabiti, J. Li, A. J. Wiemer. 2017. Cell Death Dis. 8(3):e2678. PubMed

Phosphinophosphonates and their tris-pivaloyloxymethyl prodrugs reveal a negatively cooperative butyrophilin activation mechanism. R. R. Shippy, X. Lin, S. S. Agabiti, J. Li, B. M. Zangari, B. J. Foust, M. M. Poe, C. H. Hsiao, O. Vinogradova, D. F. Wiemer, and A. J. Wiemer. J Med Chem. 2017. 60(6): 2373-2382. PubMed


Novel α-substituted tropolones promote potent and selective caspase-dependent leukemia cell apoptosis. J. Li, E. R. Falcone, S. A. Holstein, A. C. Anderson, D. L. Wright, A. J. Wiemer. Pharmacol Res. 113:438-448. 2016. PubMed

Graphical abstract of Ji 2016

Synthesis and biological evaluation of santacruzamate A analogues for anti-proliferative and immunomodulatory activity. S. M. Gromek, J. A. deMayo, A. T. Maxwell, A. M. West, C. M. Pavlik, Z. Zhao, J. Li, A. J. Wiemer, A. Zweifach, M. J. Balunas. Bioorg Med Chem. 2016. PubMed

Molecular mechanisms linking geranylgeranyl diphosphate synthase to cell survival and proliferation. Agabiti SS, Liang Y, Wiemer AJ. Mol Membr Biol. 2016 Aug 18:1-11. PubMed

HMBPP analog prodrugs bypass energy-dependent uptake to promote efficient BTN3A1-mediated malignant cell lysis by Vγ9Vδ2 T lymphocyte effectors. Kilcollins AM, Li J, Hsiao CH, Wiemer AJ. J Immunol. PubMed

Evaluation of a 7-methoxycoumarin-3-carboxylic acid ester derivative as a fluorescent, cell-cleavable, phosphonate protecting group. Wiemer AJ, Shippy RR, Kilcollins AM, Li J, Hsiao CH, Barney RJ, Geng ML, Wiemer DF. Chembiochem. 2016; Jan 1;17(1):52-5. PubMed


Prodrugs of phosphonates and phosphates: crossing the membrane barrier. Wiemer AJ and Wiemer DF. Topics in Current Chemistry. 2015 360:115-60. PubMed


Synthesis of a phosphoantigen prodrug that potently activates Vγ9Vδ2 T-lymphocytes. Hsiao CH, Lin X, Barney RJ, Shippy RR, Li J, Vinogradova O, Wiemer DF, Wiemer AJ. Chem Biol. 2014 Aug 14;21(8):945-54. PubMed

Graphical abstract of Hsiao 2014

Opportunities and challenges in development of phosphoantigens as Vγ9Vδ2 T cell agonists. Wiemer DF, Wiemer AJ. Biochem Pharmacol. 2014 Jun 1;89(3):301-12. PubMed

Cyclopropene cycloadditions with annulated furans: total synthesis of (+)- and (-)-frondosin B and (+)-frondosin a. Oblak EZ, Vanheyst MD, Li J, Wiemer AJ, Wright DL. J Am Chem Soc. 2014 Mar 19;136(11):4309-15. PubMed


The focal adhesion kinase inhibitor PF-562,271 impairs primary CD4+ T cell activation.Wiemer AJ, Wernimont SA, Cung TD, Bennin DA, Beggs HE, Huttenlocher A. Biochem Pharmacol. 2013 Sep 15;86(6):770-81. PubMed

Prior to UConn

Live imaging of LFA-1-dependent T-cell motility and stop signals. Wiemer AJ, Wernimont S, Huttenlocher A. Methods Mol Biol. 2012;757:191-204. PubMed

Contact-dependent T cell activation and T cell stopping require talin1. Wernimont SA, Wiemer AJ, Bennin DA, Monkley SJ, Ludwig T, Critchley DR, Huttenlocher A. J Immunol. 2011 Dec 15;187(12):6256-67. PubMed

Geranylgeranyl diphosphate synthase: an emerging therapeutic target. Wiemer AJ, Wiemer DF, Hohl RJ. Clin Pharmacol Ther. 2011 Dec;90(6):804-12. PubMed

A live imaging cell motility screen identifies prostaglandin E2 as a T cell stop signal antagonist. Wiemer AJ, Hegde S, Gumperz JE, Huttenlocher A. J Immunol. 2011 Oct 1;187(7):3663-70. PubMed

Isoprenoid metabolism as a therapeutic target in gram-negative pathogens. Wiemer AJ, Hsiao CH, Wiemer DF.Curr Top Med Chem. 2010;10(18):1858-71. PubMed

Calpain inhibition impairs TNF-alpha-mediated neutrophil adhesion, arrest and oxidative burst. Wiemer AJ, Lokuta MA, Surfus JC, Wernimont SA, Huttenlocher A. Mol Immunol. 2010 Jan;47(4):894-902. PubMed

The intermediate enzymes of isoprenoid metabolism as anticancer targets. Wiemer AJ, Hohl RJ, Wiemer DF. Anticancer Agents Med Chem. 2009 Jun;9(5):526-42. PubMed

Quantitative determination of farnesyl and geranylgeranyl diphosphate levels in mammalian tissue. Tong H, Wiemer AJ, Neighbors JD, Hohl RJ. Anal Biochem. 2008 Jul 15;378(2):138-43. PubMed

Pivaloyloxymethyl-modified isoprenoid bisphosphonates display enhanced inhibition of cellular geranylgeranylation. Wiemer AJ, Yu JS, Shull LW, Barney RJ, Wasko BM, Lamb KM, Hohl RJ, Wiemer DF. Bioorg Med Chem. 2008 Apr 1;16(7):3652-60. PubMed

Inhibition of geranylgeranyl diphosphate synthase induces apoptosis through multiple mechanisms and displays synergy with inhibition of other isoprenoid biosynthetic enzymes. Dudakovic A, Wiemer AJ, Lamb KM, Vonnahme LA, Dietz SE, Hohl RJ. J Pharmacol Exp Ther. 2008 Mar;324(3):1028-36. PubMed

Mono- and dialkyl isoprenoid bisphosphonates as geranylgeranyl diphosphate synthase inhibitors. Wiemer AJ, Yu JS, Lamb KM, Hohl RJ, Wiemer DF. Bioorg Med Chem. 2008 Jan 1;16(1):390-9. PubMed

Synthesis of fluorescently tagged isoprenoid bisphosphonates that inhibit protein geranylgeranylation. Maalouf MA, Wiemer AJ, Kuder CH, Hohl RJ, Wiemer DF. Bioorg Med Chem. 2007 Mar 1;15(5):1959-66. PubMed

Total synthesis of (R,R,R)- and (S,S,S)-schweinfurthin F: differences of bioactivity in the enantiomeric series. Mente NR, Wiemer AJ, Neighbors JD, Beutler JA, Hohl RJ, Wiemer DF. Bioorg Med Chem Lett. 2007 Feb 15;17(4):911-5. PubMed

Digeranyl bisphosphonate inhibits geranylgeranyl pyrophosphate synthase. Wiemer AJ, Tong H, Swanson KM, Hohl RJ. Biochem Biophys Res Commun. 2007 Feb 23;353(4):921-5. PubMed

Synthesis and biological activity of isoprenoid bisphosphonates. Shull LW, Wiemer AJ, Hohl RJ, Wiemer DF. Bioorg Med Chem. 2006 Jun 15;14(12):4130-6. PubMed

Synthesis and activity of fluorescent isoprenoid pyrophosphate analogues. Kim M, Kleckley TS, Wiemer AJ, Holstein SA, Hohl RJ, Wiemer DF. J Org Chem. 2004 Nov 26;69(24):8186-93. PubMed

Stereoselective synthesis of the 5′-hydroxy-5′-phosphonate derivatives of cytidine and cytosine arabinoside. Chen X, Wiemer AJ, Hohl RJ, Wiemer DF. J Org Chem. 2002 Dec 27;67(26):9331-9. PubMed

Synthesis of phosphonate derivatives of uridine, cytidine, and cytosine arabinoside. Jung KY, Hohl RJ, Wiemer AJ, Wiemer DF. Bioorg Med Chem. 2000 Oct;8(10):2501-9. PubMed