Advances in Cyanine - Amino Acid Conjugates and Peptides for Sensing of DNA, RNA and Protein Structures

Author(s): Tamara Šmidlehner, Andrea Rožman, Ivo Piantanida*

Journal Name: Current Protein & Peptide Science

Volume 20 , Issue 11 , 2019


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Small molecule spectrophotometric probes for DNA/RNA and proteins are of the utmost importance for diagnostics in biochemical and biomedical research. Both, naturally occurring and synthetic probes, often include peptide sequence responsible for the selectivity toward the particular target; however, commercially available dyes are restricted to single point attachment to the peptide (having one reactive group). Here presented are our recent advances in the development of novel amino acidfluorophore probes, with the unique characteristic of free N- and C-terminus available for incorporation at any peptide backbone position. Intriguingly, already monomeric amino acid-fluorophores showed recognition among various DNA/RNA, whereby steric impact and contribution of halogens is systematically studied. Moreover, some dyes revealed intracellular mitochondria specificity. Further, several hetero-dimeric chromophore systems were prepared, demonstrating that synergistic effect can lead to simultaneous DNA, RNA and protein fluorimetric recognition, combined with enzyme inhibition. Also, homodimeric cyanines equipped with chlorine revealed intriguing DNA/RNA selectivity in respect to well-known parent TOTO and YOYO dyes.

Keywords: DNA/RNA recognition, protein recognition, fluorescence, cyanine - amino acid conjugate, prokin structures, homodimers.

[1]
Drummen, G.P.C. Fluorescent probes and fluorescence (microscopy) techniques - illuminating biological and biomedical research. Molecules, 2012, 17, 14067-14090.
[2]
Bernardo, P.H.; Wan, K.F.; Sivaraman, T.; Xu, J.; Moore, F.K.; Hung, A.W.; Mok, H.Y.K.; Yu, V.C.; Chai, C.L.L. Structure-activity relationship studies of phenanthridine-based Bcl-X(L) inhibitors. J. Med. Chem., 2008, 51, 6699-6710.
[3]
Demeunynck, M.; Bailly, C.; Wilson, W.D. Small Molecule DNA and RNA Binders : From Synthesis to Nucleic Acid Complexes Wiley-VCH.,
[4]
Armitage, B.A. Cyanine dye-DNA interactions: Intercalation, groove binding, and aggregation. Top. Curr. Chem., 2005, 253, 55-76.
[5]
Jan, N.; Nicke, S.; Mikael, K. The interactions between the fluorescent dye thiazole orange and DNA. Biopolymers, 1998, 46, 39-51.
[6]
Fei, X.; Gu, Y. Progress in modifications and applications of fluorescent dye probe. Prog. Nat. Sci., 2009, 19(1), 1-7.
[7]
Johansen, F.; Jacobsen, J.P. 1H NMR studies of the bis-intercalation of a homodimeric oxazole yellow dye in DNA oligonucleotides. J. Biomol. Struct. Dyn., 1998, 16(2), 205-222.
[8]
Spielmann, H.P.; Wemmer, D.E.; Jacobsen, J.P. Solution structure of a DNA complex with the fluorescent bis-intercalator TOTO determined by NMR spectroscopy. Biochemistry, 1995, 34(27), 8542-8553.
[9]
Matić, J.; Tumir, L.M.; Stojković, M.R.; Piantanida, I. Advances in peptide-based DNA/RNA-intercalators. Curr. Protein Pept. Sci., 2016, 17(2), 127-134.
[10]
Kummer, S.; Knoll, A.; Socher, E.; Bethge, L.; Herrmann, A.; Seitz, O. PNA FIT-probes for the dual color imaging of two viral mRNA targets in influenza H1N1 infected live cells. Bioconjug. Chem., 2012, 23(10), 2051-2060.
[11]
Hövelmann, F.; Gaspar, I.; Ephrussi, A.; Seitz, O. Brightness enhanced DNA FIT-probes for wash-free RNA imaging in tissue. J. Am. Chem. Soc., 2013, 135(50), 19025-19032.
[12]
Hövelmann, F.; Gaspar, I.; Loibl, S.; Ermilov, E.A.; Röder, B.; Wengel, J.; Ephrussi, A.; Seitz, O. Brightness through local constraint-LNA-enhanced FIT hybridization probes for in vivo ribonucleotide particle tracking. Angew. Chemie. Int. Ed., 2014, 53(42), 11370-11375.
[13]
Mahon, K.P.; Roy, M.D.; Carreon, J.R. Prestwich, E.G.; Rouge, J.L.; Shin, S.; Kelley, S.O. Tunable DNA cleavage by intercalating peptidoconjugates. ChemBioChem, 2006, 7(5), 766-773.
[14]
Thompson, B. Synthesis, photophysical effects, and DNA targeting properties of oxazole yellow-peptide bioconjugates. Bioconjug. Chem., 2006, 17, 507-513.
[15]
Šmidlehner, T.; Piantanida, I. Novel DNA / RNA-targeting amino acid beacon for the versatile incorporation at any position within the peptide backbone. Amino Acids, 2017, 49(8), 1381-1388.
[16]
Šmidlehner, T.; Kurutos, A.; Slade, J.; Belužić, R.; Ang, D.L.; Rodger, A.; Piantanida, I. Versatile cyanine-click-amino acid conjugates showing one-atom- influenced recognition of DNA / RNA secondary structure and mitochondrial localization in living cells. Eur. J. Org. Chem., 2018, 14, 1682-1692.
[17]
Šmidlehner, T.; Badovinac, M.; Piantanida, I. Pyrene – cyanine conjugates as multipurpose fluorescent probes for non-covalent recognition of DS-DNA, RNA and proteins. New J. Chem., 2018, 42, 6655-6663.
[18]
Matić, J.; Šupljika, F.; Tir, N.; Piotrowski, P.; Schmuck, C.; Abramić, M.; Piantanida, I.; Tomić, S. Guanidiniocarbonyl-pyrrole-aryl conjugates as inhibitors of human dipeptidyl peptidase III: Combined experimental and computational study. RSC Adv, 2016, 6(86), 83044-83052.
[19]
Šmidlehner, T.; Karačić, Z.; Tomic, S.; Schmuck, C.; Piantanida, I. Fluorescent cyanine-guanidiniocarbonyl-pyrrole conjugate with pH- Dependent DNA / RNA recognition and DPP III fluorescent labelling and inhibition properties. Monatshefte fur. Chemie., 2018, 149(7), 1307-1313.
[20]
Fürstenberg, A.; Julliard, M.D.; Deligeorgiev, T.G.; Gadjev, N.I.; Vasilev, A.A.; Vauthey, E. Ultrafast excited-state dynamics of DNA fluorescent intercalators: New insight into the fluorescence enhancement mechanism. J. Am. Chem. Soc., 2006, 128(23), 7661-7669.
[21]
Rožman, A.; Crnolatac, I.; Deligeorgiev, T.; Piantanida, I. Strong impact of chloro substituent on TOTO and YOYO Ds-DNA/RNA sensing. J. Lumin., 2019, 205, 87-96.
[22]
Teo, Y.N.; Kool, E.T. Polyfluorophore excimers and exciplexes as FRET donors in DNA. Bioconjug. Chem., 2009, 20(12), 2371-2380.
[23]
Šmidlehner, T.; Piantanida, I.; Pescitelli, G. Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids - tutorial. Beilstein J. Org. Chem., 2018, 14, 84-105.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 11
Year: 2019
Published on: 23 October, 2019
Page: [1040 - 1045]
Pages: 6
DOI: 10.2174/1389203720666190513084102
Price: $65

Article Metrics

PDF: 23
HTML: 2
EPUB: 1
PRC: 1