INTERACTION BETWEEN SYNTHETIC ANALOGUES OF QUINOXALINE ANTIBIOTICS AND NUCLEIC ACIDS: ROLE OF THE DISULPHIDE CROSS‐BRIDGE AND <scp>d</scp>‐AMINO ACID CENTRES IN DES‐<i>N</i>‐TETRAMETHYL‐TRIOSTIN A

Fox, Keith R.; Olsen, Richard K.; Waring, Michael J.; Chakravarty, Prasun K.

doi:10.1111/j.1476-5381.1980.tb10900.x

Cited by 15 publications

(6 citation statements)

References 22 publications

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“…In the event neither of these notions proved to be correct. Most probably the conformation of the depsipeptide in solution is different from that of either triostin A or ANDEM; the asymmetric peptide ring may be twisted in such a way that the quinoxaline chromophores are no longer positioned roughly parallel to allow for bifunctional intercalation into the DNA helixlike the situation previously postulated for L-serine-containing analogues of TANDEM [6,13].…”

Section: Discussion [N-meval4]tandemmentioning

confidence: 98%

“…The cysteine -NH groups do not therefore appear to play an important role in either holding the peptide portion of the antibiotic in any particular conformation, or in determining the sequence-selectivity of the ligand. In fact [Ala3, Ala7]TANDEM, a compound lacking a cross-bridge altogether, has been shown to interact with DNA (albeit weakly) and again displays the same AT specificity as does TANDEM [13]. It seems likely that the function of the cysteine residues in providing the cross-bridge is to restrict the conformational flexibility of the peptide ring so as to reduce unfavourable entropy terms in the binding reaction, rather than to participate in direct interactions with functional groups on the DNA.…”

Section: Discussion [N-meval4]tandemmentioning

confidence: 99%

“…The other analogue [N-MeCys3, N-MeCys7] TANDEM permits the role of the functional groups on the amino acid residues forming the cross-bridge to be investigated. It has previously been shown that the cross-bridge itself is not instrumental in determining the sequence-specificity of these antibiotics since [Ala3, Ala7]TANDEM, a compound without a cross-bridge, retains the AT specificity of TANDEM [13]. However, while the NH groups of the cysteine residues have not previously been implicated as determinants of sequence-selectivity, there is no information concerning their role, if any, in [IA binding.…”

Section: Introductionmentioning

confidence: 99%

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DNA sequence recognition by under-methylated analogues of triostin A

Low¹,

Fox²,

Olsen

et al. 1986

Nucl Acids Res

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Two new analogues of TANDEM (des-N-tetramethyl triostin A) have been synthesised in an effort to elucidate the molecular basis of DNA nucleotide sequence recognition in this series of compounds. Their binding preferences have been investigated by DNAase I footprinting and differential inhibition of restriction nuclease attack. The presence of a single N-methyl group on only one valine residue (in [N-MeVal4] TANDEM) abolishes the ability to recognise DNA, presumably because this antibiotic analogue has suffered an unfavourable conformational change in the depsipeptide ring. A bis-methylated analogue, [N-MeCys3, N-MeCys7]TANDEM, was found to interact quite strongly with DNA and afforded binding sites, rich in AT residues, identical to those of TANDEM. Footprinting with various DNA fragments of known sequence showed that this analogue recognises sequences containing the dinucleotide TpA, although we cannot exclude the possibility that it binds to ApT as well. [N-MeCys3, N-MeCys7]TANDEM inhibits cutting by RsaI, a restriction enzyme that recognises GTAC but not by Sau3AI which recognises GATC. This provides further supportive evidence that the ligand (and, by extension, TANDEM itself) prefers binding to sequences containing the dinucleotide step TpA.

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Section: Discussion [N-meval4]tandemmentioning

confidence: 98%

Section: Discussion [N-meval4]tandemmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNA sequence recognition by under-methylated analogues of triostin A

Low¹,

Fox²,

Olsen

et al. 1986

Nucl Acids Res

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“…Regarding the interaction of artificial molecules with poly(rA), Manzini et al [44] found that the compound known as 4',6diamidino-2-phenylindole dihydrochloride (DAPI, Figure 7) can bind double helical poly(rA). Similarly, synthetic analogues of quinoxaline are also able to bind poly(rA)•poly(rU) complexes [45], while other artificial compounds such as ethidium salts, quinacrine, and proflavine proved to be efficient binders of single-stranded poly(rA) capable of inducing self-structures of such RNA. This characteristic is absent in the compound Hoechst 33258 that acts as a poly(rA) binder, but is unable to provoke structural organization in the same RNA [46].…”

Section: Synthetic Organic Moleculesmentioning

confidence: 99%

Natural and artificial binders of polyriboadenylic acid and their effect on RNA structure

Roviello¹,

Musumeci²,

Roviello³

et al. 2016

Nano Online

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The employment of molecular tools with nucleic acid binding ability to specifically control crucial cellular functions represents an important scientific area at the border between biochemistry and pharmaceutical chemistry. In this review we describe several molecular systems of natural or artificial origin, which are able to bind polyriboadenylic acid (poly(rA)) both in its single-stranded or structured forms. Due to the fundamental role played by the poly(rA) tail in the maturation and stability of mRNA, as well as in the initiation of the translation process, compounds able to bind this RNA tract, influencing the mRNA fate, are of special interest for developing innovative biomedical strategies mainly in the field of anticancer therapy. 1338 Review Polyadenylation in RNA processing Polyadenylation is part of the RNA processing pathway that leads to the production of mature mRNA molecules (Figure 1) [1]. The poly(rA) tail is a long chain of adenine nucleotides that is added to the 3'-end of the primary RNA transcript (pre-mRNA) during the transcription of a specific gene in eukary-otic cells. The pre-mRNA molecule undergoes three main processes (5'-capping, 3'-polyadenylation and RNA splicing) occurring in the cell nucleus before the RNA is exported to the cytoplasm for translation (Figure 1). The pre-mRNA undergoes capping co-transcriptionally as it is released from the RNA

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“…Similarly, synthetic analogues of quinoxaline are also able to bind poly(rA)·poly(rU) complexes [ 45 ], while other artificial compounds such as ethidium salts, quinacrine, and proflavine proved to be efficient binders of single-stranded poly(rA) capable of inducing self-structures of such RNA. This characteristic is absent in the compound Hoechst 33258 that acts as a poly(rA) binder, but is unable to provoke structural organization in the same RNA [ 46 ].…”

Section: Reviewmentioning

confidence: 99%

Natural and artificial binders of polyriboadenylic acid and their effect on RNA structure

Roviello

Musumeci

Roviello

et al. 2015

Beilstein J. Nanotechnol.

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SummaryThe employment of molecular tools with nucleic acid binding ability to specifically control crucial cellular functions represents an important scientific area at the border between biochemistry and pharmaceutical chemistry. In this review we describe several molecular systems of natural or artificial origin, which are able to bind polyriboadenylic acid (poly(rA)) both in its single-stranded or structured forms. Due to the fundamental role played by the poly(rA) tail in the maturation and stability of mRNA, as well as in the initiation of the translation process, compounds able to bind this RNA tract, influencing the mRNA fate, are of special interest for developing innovative biomedical strategies mainly in the field of anticancer therapy.

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INTERACTION BETWEEN SYNTHETIC ANALOGUES OF QUINOXALINE ANTIBIOTICS AND NUCLEIC ACIDS: ROLE OF THE DISULPHIDE CROSS‐BRIDGE AND d‐AMINO ACID CENTRES IN DES‐N‐TETRAMETHYL‐TRIOSTIN A

Abstract: I [Ala3, Ala'] TANDEM is an analogue of des-N-tetramethyl-triostin A (TANDEM) in which both L-Cys residues of the octapeptide ring are replaced by L-Ala; accordingly it lacks the disulphide cross-bridge which limits the conformational flexibility of TANDEM.

Cited by 15 publications

References 22 publications

DNA sequence recognition by under-methylated analogues of triostin A

DNA sequence recognition by under-methylated analogues of triostin A

Natural and artificial binders of polyriboadenylic acid and their effect on RNA structure

Natural and artificial binders of polyriboadenylic acid and their effect on RNA structure

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