Andrew M Whitney's research while affiliated with University of Cambridge and other places

Publications (4)

Article
Reversible disulfide chemistry is used to identify ligands that stabilize either duplex or quadruplex DNA secondary structures from a dynamic combinatorial library of polyamide building blocks (example structure shown). Double-stranded DNA induces a larger amplification than quadruplex DNA, in accordance with the selectivity of the ligands for each...
Article
The tetramolecular PNA quadruplex motif has been probed using a dynamic covalent chemistry (DCC) approach to create and characterize a bimolecular PNA quadruplex.
Article
G-Quadruplex-DNA-bindende Liganden aus einer kleinen dynamischen Bibliothek (DCL) wurden mittels reversibler Disulfid-Bindungsbildung identifiziert (siehe Schema). Es wurde gezeigt, dass das biologische makromolekulare Target eine Gleichgewichtsverschiebung induziert. Die Quadruplex-DNA-Bindung zweier amplifizierter Spezies konnte mit Oberflächenpl...
Article
Here we report the synthesis of a novel PNA based neocuproine.Zn RNA cleaving agent; we demonstrate that such agents sequence specifically cleave a synthetic RNA target and in particular the RNA component of human telomerase.

Citations

... The cleavage of long mRNA transcripts causes additional difficulties because the secondary and tertiary RNA structures would prevent the binding of ss-aRNases with it. Since the review of Lonnberg [21], when there were only a few papers, where metal-dependent ss-aRNases cleaved biologically relevant RNA transcripts of human c-raf-1, telomerase and apolipoprotein E gene [46,73,74], the situation has not changed dramatically. The ss-aRNase based on tris(2-aminobenzimidazole) is one of the few examples showed the ability to efficiently cleave long structured biologically relevant RNAs representing 155, 412 and 430-mer RNA transcripts derived from the 3′-UTR of the PIM1 mRNA [32]. ...
... The first application of DCC to the search of G-quadruplex ligands was described by Balasubramanian et al. and employed the disulfide exchange. 124 A relatively simple system was composed by the acridone derivative A (that was supposed to interact with external Gtetrads of G4s by π-stacking) and tetrapeptide FRHR P (presumable loop/groove-binder) in a buffer that contained excess of both oxidized (G) and reduced (G-G) forms of glutathione (DCL1, Scheme 4). When reaction reached the equilibrium it was stopped by lowering pH value to 2 and the "frozen" libraries were analyzed by HPLC. ...
... Other G4 structures were observed, with the PNA sequence G4T4G4 involving both DNA-PNA hybrid structures (PNA2−DNA2 G4) [85] and pure PNA self-assemblies including both dimeric and tetrameric G4s, with a preference for the former [86]. PNAs were also found to form bimolecular [87] and unimolecular antiparallel G4 [88]. G-rich PNAs bind to homologous nucleic acids to form hetero-G4s, but can also bind to complementary cytosine-rich DNA and RNA sequences to form hetero-duplexes. ...
... 124 Another example, also reported by the same team, employed the peptidic spacing containing one, two or three N-methylpyrrole heterocycles that mimic the previously mentioned distamycin ligand (page 30) that binds DNA duplexes and G-quadruplexes (DCL2, Figure 27). 125 The reaction was performed in the presence of large excess of glutathione to avoid selfassembly of P3 (up to 75% in low glutathione buffer). In the presence of human telomeric Gquadruplex, disulfides P2-P3 and P3-P3 were amplified (130 and 140%, respectively). ...