U.S. Department of Health and Human Services
Daniel Appella

 Contact Info

Tel: 301-451-1052
Email: appellad@niddk.nih.gov

 Select Experience

  • Assistant ProfessorNorthwestern University2001-2004
  • Postdoctoral FellowMassachusetts Institute of Technology1998 – 2001
  • Ph.D.University of Wisconsin-Madison1998

 Related Links

  • Chemistry/Chemical Biology


A selection of recent and significant publications can be viewed below.

Hartman TL, Yang L, Helfrick AN, Hassink M, Shank NI, George Rosenker K, Scerba MT, Saha M, Hughes E, Wang AQ, Xu X, Gupta P, Buckheit RW Jr, Appella DH. Preclinical evaluation of a mercaptobenzamide and its prodrug for NCp7-targeted inhibition of human immunodeficiency virus. Antiviral Res. 2016 Aug 25; 134 (134; 2016 Aug 25):216-225. [Full Text/Abstract]
Gupta P, Rastede EE, Appella DH. Multivalent (L)Kγ-PNA oligomers bind to a human telomere DNA G-rich sequence to form quadruplexes. Bioorg Med Chem Lett. 2015 Jul 29; 25 (25; 2015 Jul 29; 21):4757-60. [Full Text/Abstract]
Ugaonkar SR, Clark JT, English LB, Johnson TJ, Buckheit KW, Bahde RJ, Appella DH, Buckheit RW Jr, Kiser PF. An Intravaginal Ring for the Simultaneous Delivery of an HIV-1 Maturation Inhibitor and Reverse-Transcriptase Inhibitor for Prophylaxis of HIV Transmission. J Pharm Sci. 2015 Jul 6; 104 (104; 2015 Jul 6; 10):3426-39. [Full Text/Abstract]
Dix AV, Conroy JL, George Rosenker KM, Sibley DR, Appella DH. PNA-Based Multivalent Scaffolds Activate the Dopamine D2 Receptor. ACS Med Chem Lett. 2015 Apr 9; 6 (6; 4; 2015 Apr 9):425-9. [Full Text/Abstract]
Gaynutdinov TI, Englund EA, Appella DH, Onyshchenko MI, Neumann RD, Panyutin IG. G-quadruplex formation between G-rich PNA and homologous sequences in oligonucleotides and supercoiled plasmid DNA. Nucleic Acid Ther. 2015 Feb 4; 25 (25; 2; 2015 Feb 4):78-84. [Full Text/Abstract]
Zhao C, Hoppe T, Setty MK, Murray D, Chun TW, Hewlett I, Appella DH. Quantification of plasma HIV RNA using chemically engineered peptide nucleic acids. Nat Commun. 2014 Oct 6; 5 (2014 Oct 6; 5):5079. [Full Text/Abstract]
Englund EA, Gupta P, Micklitsch CM, Onyshchenko MI, Remeeva E, Neumann RD, Panyutin IG, Appella DH. PPG peptide nucleic acids that promote DNA guanine quadruplexes. Chembiochem. 2014 Jul 8; 15 (15; 13; 2014 Jul 8):1887-90. [Full Text/Abstract]
Dix AV, Moss SM, Phan K, Hoppe T, Paoletta S, Kozma E, Gao ZG, Durell SR, Jacobson KA, Appella DH. Programmable Nanoscaffolds That Control Ligand Display to a G-Protein-Coupled Receptor in Membranes To Allow Dissection of Multivalent Effects. J Am Chem Soc. 2014 Aug 25; 136 (35; 2014 Aug 25; 136):12296-303. [Full Text/Abstract]
Englund EA, Zhang N, Appella DH. Cyclopentane peptide nucleic acids. Methods Mol Biol. 2014; 1050 (2014; 1050):13-8. [Full Text/Abstract]
Ranjan N, Kumar S, Watkins D, Wang D, Appella DH, Arya DP. Recognition of HIV-TAR RNA using neomycin-benzimidazole conjugates. Bioorg Med Chem Lett. 2013 Oct 15; 23 (20; 23; 2013 Oct 15):5689-93. [Full Text/Abstract]
Simister PC, Luccarelli J, Thompson S, Appella DH, Feller SM, Hamilton AD. Novel inhibitors of a Grb2 SH3C domain interaction identified by a virtual screen. Bioorg Med Chem. 2013 Jul 15; 21 (14; 2013 Jul 15; 21):4027-33. [Full Text/Abstract]
Micklitsch CM, Oquare BY, Zhao C, Appella DH. Cyclopentane-peptide nucleic acids for qualitative, quantitative, and repetitive detection of nucleic acids. Anal Chem. 2013 Jan 2; 85 (85; 2013 Jan 2; 1):251-7. [Full Text/Abstract]
Kumar S, Kellish P, Robinson WE Jr, Wang D, Appella DH, Arya DP. Click dimers to target HIV TAR RNA conformation. Biochemistry. 2012 Mar 20; 51 (2012 Mar 20; 51; 11):2331-47. [Full Text/Abstract]
Englund EA, Wang D, Fujigaki H, Sakai H, Micklitsch CM, Ghirlando R, Martin-Manso G, Pendrak ML, Roberts DD, Durell SR, Appella DH. Programmable multivalent display of receptor ligands using peptide nucleic acid nanoscaffolds. Nat Commun. 2012 Jan 10; 3 (2012 Jan 10; 3):614. [Full Text/Abstract]
Panyutin IG, Onyshchenko MI, Englund EA, Appella DH, Neumann RD. Targeting DNA G-quadruplex structures with peptide nucleic acids. Curr Pharm Des. 2012; 18 (2012; 14; 18):1984-91. [Full Text/Abstract]
Pokorski JK, Appella DH. Combinatorial Synthesis, Screening, and Binding Studies of Highly Functionalized Polyamino-amido Oligomers for Binding to Folded RNA. J Nucleic Acids. 2012; 2012 (2012):971581. [Full Text/Abstract]
Onyshchenko MI, Gaynutdinov TI, Englund EA, Appella DH, Neumann RD, Panyutin IG. Quadruplex formation is necessary for stable PNA invasion into duplex DNA of BCL2 promoter region. Nucleic Acids Res. 2011 Sep 1; 39 (16; 39; 2011 Sep 1):7114-23. [Full Text/Abstract]
Bahde RJ, Appella DH, Trenkle WC. A one-pot preparation of N-2-mercaptobenzoyl-amino amides. Tetrahedron Lett. 2011 Aug 10; 52 (32; 2011 Aug 10; 52):4103-4105. [Full Text/Abstract]
Hayashi R, Tanoue K, Durell SR, Chatterjee DK, Jenkins LM, Appella DH, Appella E. Optimization of a cyclic peptide inhibitor of Ser/Thr phosphatase PPM1D (Wip1). Biochemistry. 2011 May 31; 50 (50; 21; 2011 May 31):4537-49. [Full Text/Abstract]
Liu Y, Norton JT, Witschi MA, Xu Q, Lou G, Wang C, Appella DH, Chen Z, Huang S. Methoxyethylamino-numonafide is an efficacious and minimally toxic amonafide derivative in murine models of human cancer. Neoplasia. 2011 May; 13 (13; 5; 2011 May):453-60. [Full Text/Abstract]
Macadangdang B, Zhang N, Lund PE, Marple AH, Okabe M, Gottesman MM, Appella DH, Kimchi-Sarfaty C. Inhibition of multidrug resistance by SV40 pseudovirion delivery of an antigene peptide nucleic acid (PNA) in cultured cells. PLoS One. 2011 Mar 22; 6 (6; 2011 Mar 22; 3):e17981. [Full Text/Abstract]
Miller Jenkins LM, Ott DE, Hayashi R, Coren LV, Wang D, Xu Q, Schito ML, Inman JK, Appella DH, Appella E. Small-molecule inactivation of HIV-1 NCp7 by repetitive intracellular acyl transfer. Nat Chem Biol. 2010 Dec; 6 (6; 2010 Dec; 12):887-9. [Full Text/Abstract]
Iera JA, Jenkins LM, Kajiyama H, Kopp JB, Appella DH. Solid-phase synthesis and screening of N-acylated polyamine (NAPA) combinatorial libraries for protein binding. Bioorg Med Chem Lett. 2010 Nov 15; 20 (20; 2010 Nov 15; 22):6500-3. [Full Text/Abstract]
Zhang N, Appella DH. Advantages of peptide nucleic acids as diagnostic platforms for detection of nucleic acids in resource-limited settings. J Infect Dis. 2010 Apr 15; 201 Suppl 1 (201 Suppl 1; 2010 Apr 15):S42-5. [Full Text/Abstract]
Appella DH. Directed evolution: overcoming biology's limitations. Nat Chem Biol. 2010 Feb; 6 (6; 2; 2010 Feb):87-8. [Full Text/Abstract]
Wang D, Iera J, Baker H, Hogan P, Ptak R, Yang L, Hartman T, Buckheit RW Jr, Desjardins A, Yang A, Legault P, Yedavalli V, Jeang KT, Appella DH. Multivalent binding oligomers inhibit HIV Tat-TAR interaction critical for viral replication. Bioorg Med Chem Lett. 2009 Dec 15; 19 (19; 2009 Dec 15; 24):6893-7. [Full Text/Abstract]
Hayashi R, Wang D, Hara T, Iera JA, Durell SR, Appella DH. N-acylpolyamine inhibitors of HDM2 and HDMX binding to p53. Bioorg Med Chem. 2009 Dec 1; 17 (2009 Dec 1; 23; 17):7884-93. [Full Text/Abstract]
Appella DH. Non-natural nucleic acids for synthetic biology. Curr Opin Chem Biol. 2009 Dec; 13 (13; 5-6; 2009 Dec):687-96. [Full Text/Abstract]
Waters ML, Appella DH. Mimicking nature: from fundamentals to applications. Curr Opin Chem Biol. 2009 Dec; 13 (13; 5-6; 2009 Dec):641-2. [Full Text/Abstract]
Onyshchenko MI, Gaynutdinov TI, Englund EA, Appella DH, Neumann RD, Panyutin IG. Stabilization of G-quadruplex in the BCL2 promoter region in double-stranded DNA by invading short PNAs. Nucleic Acids Res. 2009 Dec; 37 (37; 22; 2009 Dec):7570-80. [Full Text/Abstract]
Rossi M, Bang JK, Mazur S, Iera JA, Phillips DC, Zambetti GP, Appella DH. Induction of apoptosis promoted by Bang52; a small molecule that downregulates Bcl-x(L). Bioorg Med Chem Lett. 2009 May 1; 19 (2009 May 1; 19; 9):2429-34. [Full Text/Abstract]
Xu Q, Appella DH. Aziridination of aliphatic alkenes catalyzed by N-heterocyclic carbene copper complexes. Org Lett. 2008 Apr 3; 10 (7; 10; 2008 Apr 3):1497-500. [Full Text/Abstract]
Bang J, Yamaguchi H, Durell SR, Appella E, Appella DH. A small molecular scaffold for selective inhibition of Wip1 phosphatase. ChemMedChem. 2008 Feb; 3 (2; 3; 2008 Feb):230-2. [Full Text/Abstract]
Norton JT, Witschi MA, Luong L, Kawamura A, Ghosh S, Stack MS, Sim E, Avram MJ, Appella DH, Huang S. Synthesis and anticancer activities of 6-amino amonafide derivatives. Anticancer Drugs. 2008 Jan; 19 (19; 2008 Jan; 1):23-36. [Full Text/Abstract]
Zhang N, Appella DH. Colorimetric detection of anthrax DNA with a Peptide nucleic acid sandwich-hybridization assay. J Am Chem Soc. 2007 Jul 11; 129 (27; 2007 Jul 11; 129):8424-5. [Full Text/Abstract]
Pokorski JK, Jenkins LM, Feng H, Durell SR, Bai Y, Appella DH. Introduction of a triazole amino acid into a peptoid oligomer induces turn formation in aqueous solution. Org Lett. 2007 Jun 7; 9 (2007 Jun 7; 12; 9):2381-3. [Full Text/Abstract]
Englund EA, Appella DH. Gamma-substituted peptide nucleic acids constructed from L-lysine are a versatile scaffold for multifunctional display. Angew Chem Int Ed Engl. 2007; 46 (46; 9; 2007):1414-8. [Full Text/Abstract]
Englund EA, Xu Q, Witschi MA, Appella DH. PNA-DNA duplexes, triplexes, and quadruplexes are stabilized with trans-cyclopentane units. J Am Chem Soc. 2006 Dec 27; 128 (128; 2006 Dec 27; 51):16456-7. [Full Text/Abstract]
Xu Q, Appella DH. Practical synthesis of trans-tert-butyl-2-aminocyclopentylcarbamate and resolution of enantiomers. J Org Chem. 2006 Oct 27; 71 (71; 2006 Oct 27; 22):8655-7. [Full Text/Abstract]
Hara T, Durell SR, Myers MC, Appella DH. Probing the structural requirements of peptoids that inhibit HDM2-p53 interactions. J Am Chem Soc. 2006 Feb 15; 128 (128; 2006 Feb 15; 6):1995-2004. [Full Text/Abstract]
Witschi MA, Pokorski JK, Appella DH. Peptide nucleic acid microarrays made with (S,S)-trans-cyclopentane-constrained peptide nucleic acids. Methods Enzymol. 2006; 410 (410; 2006):189-200. [Full Text/Abstract]
Englund EA, Appella DH. Synthesis of gamma-substituted peptide nucleic acids: a new place to attach fluorophores without affecting DNA binding. Org Lett. 2005 Aug 4; 7 (16; 7; 2005 Aug 4):3465-7. [Full Text/Abstract]
Myers MC, Wang J, Iera JA, Bang JK, Hara T, Saito S, Zambetti GP, Appella DH. A new family of small molecules to probe the reactivation of mutant p53. J Am Chem Soc. 2005 May 4; 127 (127; 17; 2005 May 4):6152-3. [Full Text/Abstract]
Guler MO, Pokorski JK, Appella DH, Stupp SI. Enhanced oligonucleotide binding to self-assembled nanofibers. Bioconjug Chem. 2005 May-Jun; 16 (16; 2005 May-Jun; 3):501-3. [Full Text/Abstract]
Pokorski JK, Nam JM, Vega RA, Mirkin CA, Appella DH. Cyclopentane-modified PNA improves the sensitivity of nanoparticle-based scanometric DNA detection. Chem Commun (Camb). 2005 Apr 28; (16; 2005 Apr 28):2101-3. [Full Text/Abstract]
Myers MC, Pokorski JK, Appella DH. Peptide nucleic acids with a flexible secondary amine in the backbone maintain oligonucleotide binding affinity. Org Lett. 2004 Dec 9; 6 (25; 2004 Dec 9; 6):4699-702. [Full Text/Abstract]
Pokorski JK, Witschi MA, Purnell BL, Appella DH. (S,S)-trans-cyclopentane-constrained peptide nucleic acids. a general backbone modification that improves binding affinity and sequence specificity. J Am Chem Soc. 2004 Nov 24; 126 (46; 126; 2004 Nov 24):15067-73. [Full Text/Abstract]
Lawton GR, Appella DH. Nonionic side chains modulate the affinity and specificity of binding between functionalized polyamines and structured RNA. J Am Chem Soc. 2004 Oct 13; 126 (2004 Oct 13; 126; 40):12762-3. [Full Text/Abstract]
Englund EA, Gopi HN, Appella DH. An efficient synthesis of a probe for protein function: 2,3-diaminopropionic acid with orthogonal protecting groups. Org Lett. 2004 Jan 22; 6 (2004 Jan 22; 6; 2):213-5. [Full Text/Abstract]
Myers MC, Witschi MA, Larionova NV, Franck JM, Haynes RD, Hara T, Grajkowski A, Appella DH. A cyclopentane conformational restraint for a peptide nucleic acid: design, asymmetric synthesis, and improved binding affinity to DNA and RNA. Org Lett. 2003 Jul 24; 5 (2003 Jul 24; 15; 5):2695-8. [Full Text/Abstract]