Effect of olivomycin and echinomycin on initiation and growth of RNA chains catalyzed by RNA polymerase

Gause, G.G.; Loshkareva, N.P.; Zbarsky, I. B.

doi:10.1016/0005-2787(68)90394-8

Cited by 15 publications

(6 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It belongs to the class of compounds known as DNA bisintercalators,38 where the compound binds to the minor groove of DNA in a sequence‐specific fashion with a central two base‐pair (bp) sequence 5′‐CG‐3′ and inserting its quinoxaline chromophores between the bases of the DNA by forming a two‐base‐pair sandwich (Figure 5). Echinomycin initiates apoptosis in cancer cells following the formation of the complex with DNA and subsequently inhibiting the transcription by blocking RNA polymerase 39. Although echinomycin was brought to clinical trials as a cancer chemotherapeutic by the NCI several years ago, minimal or no antitumor activity was found in phase II clinical trials and it caused severe side effects, such as nausea, vomiting, reversible liver enzyme abnormalities 40.…”

Section: N‐methylated Peptides Of Natural Originmentioning

confidence: 99%

N‐Methylation of Peptides and Proteins: An Important Element for Modulating Biological Functions

2012

View full text Add to dashboard Cite

N-Methylation is one of the simplest chemical modifications often occurring in peptides and proteins of prokaryotes and higher eukaryotes. Over years of evolution, nature has employed N-methylation of peptides as an ingenious technique to modulate biological function, often as a mode of survival through the production of antibiotics. This small structural change can not only mobilize large protein complexes (as in the histone methylation), but also inhibits the action of enzymes by selective recognition of protein-protein interaction surfaces. In recent years through the advancement in synthetic approaches, the potential of N-methylation has begun to be revealed, not only in modulating biological activity and selectivity as well as pharmacokinetic properties of peptides, but also in delivering novel drugs. Herein, we summarize the current knowledge of the versatility of N-methylation in modulating biological, structural, and pharmacokinetic properties of peptides.

show abstract

Section: N‐methylated Peptides Of Natural Originmentioning

confidence: 99%

N‐Methylation of Peptides and Proteins: An Important Element for Modulating Biological Functions

2012

View full text Add to dashboard Cite

show abstract

“…This type of targeting towards DNA minor groove explains the antitumor and antimicrobial bioactivities found in all family members, as this bisintercalation blocks core cell processes as those dependent on RNA polymerase, therefore inhibiting transcription [86,87]. …”

Section: Bioactivity Of Bisintercalator Compoundsmentioning

confidence: 99%

Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds

et al. 2014

View full text Add to dashboard Cite

Diverse actinomycetes produce a family of structurally and biosynthetically related non-ribosomal peptide compounds which belong to the chromodepsipeptide family. These compounds act as bisintercalators into the DNA helix. They give rise to antitumor, antiparasitic, antibacterial and antiviral bioactivities. These compounds show a high degree of conserved modularity (chromophores, number and type of amino acids). This modularity and their high sequence similarities at the genetic level imply a common biosynthetic origin for these pathways. Here, we describe insights about rules governing this modular biosynthesis, taking advantage of the fact that nowadays five of these gene clusters have been made public (thiocoraline, triostin, SW-163 and echinomycin/quinomycin). This modularity has potential application for designing and producing novel genetic engineered derivatives, as well as for developing new chemical synthesis strategies. These would facilitate their clinical development.

show abstract

“…For example, thiocoraline inhibits DNA polymerase R, 145,146 while echinomycin disrupts RNA polymerase. 147 The chromophores that bisintercalate into the DNA are quinoxaline or quinoline ring structures that can be decorated with hydroxyl methoxy groups. While there are no quinoxaline antibiotics currently in clinical use, members of this natural product family are of medical interest because they have antitumor activity (echinomycin, thiocoraline) and anti-HIV potential (luzopeptins, quinoxapeptins).…”

Section: Daptomycin (Type a Linear Nrps)mentioning

confidence: 99%

Nonribosomal Peptide Synthetases Involved in the Production of Medically Relevant Natural Products

et al. 2008

View full text Add to dashboard Cite

Natural products biosynthesized wholly or in part by nonribosomal peptide synthetases (NRPSs) are some of the most important drugs currently used clinically for the treatment of a variety of diseases. Since the initial research into NRPSs in the early 1960s, we have gained considerable insights into the mechanism by which these enzymes assemble these natural products. This review will present a brief history of how the basic mechanistic steps of NRPSs were initially deciphered and how this information has led us to understand how nature modified these systems to generate the enormous structural diversity seen in nonribosomal peptides. This review will also briefly discuss how drug development and discovery are being influenced by what we have learned from nature about nonribosomal peptide biosynthesis.

show abstract

Effect of olivomycin and echinomycin on initiation and growth of RNA chains catalyzed by RNA polymerase

Cited by 15 publications

References 3 publications

N‐Methylation of Peptides and Proteins: An Important Element for Modulating Biological Functions

N‐Methylation of Peptides and Proteins: An Important Element for Modulating Biological Functions

Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds

Nonribosomal Peptide Synthetases Involved in the Production of Medically Relevant Natural Products

Contact Info

Product

Resources

About