Natural product diversification using a non-natural cofactor analogue of S-adenosyl-L-methionine

Journal of the American Chemical Society
Changsheng ZhangScott R Rajski

Abstract

Adenosine analogues bearing either 5'-aziridine or 5'-N-mustard electrophiles are methyltransferase-dependent DNA alkylating agents. We present here a novel synthetic cofactor bearing a pendant 5'-amino acid N-mustard. Unlike previously studied synthetic cofactors, this material is very efficiently used by the natural product biosynthetic enzyme rebeccamycin methyltransferase (RebM) to generate a number of new rebeccamycin analogues. These data promote the notion that natural product methyltransferases can be used with non-natural cofactors to enhance the molecular diversity of natural product analogues for drug discovery. To our knowledge, this is the first documentation of a biological methyltransferase, other than DNA methyltransferases, that can exploit such synthetic cofactors.

References

Dec 26, 2003·Chembiochem : a European Journal of Chemical Biology·Jon S ThorsonDimitar B Nikolov
Feb 18, 2004·Current Topics in Medicinal Chemistry·T DavidAnne Cooke
Mar 22, 2005·Nucleic Acids Research·Lindsay R Comstock, Scott R Rajski
May 20, 2005·Organic Letters·Rachel L Weller, Scott R Rajski

❮ Previous
Next ❯

Citations

Mar 2, 2011·Accounts of Chemical Research·I Ayelen RamalloRicardo L E Furlan
Apr 7, 2012·Chemical Reviews·Arndt W SchmidtHans-Joachim Knölker
Nov 23, 2006·Natural Product Reports·César SánchezJosé A Salas
Jul 24, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jaeheon LeeDouglas A Mitchell
May 27, 2008·The Journal of Biological Chemistry·Shanteri SinghJon S Thorson
Dec 29, 2006·Proceedings of the National Academy of Sciences of the United States of America·Silvia N LópezRicardo L E Furlan
Mar 3, 2009·Current Opinion in Chemical Biology·José A Salas, Carmen Méndez
Apr 7, 2007·Trends in Microbiology·José A Salas, Carmen Méndez
May 4, 2011·Proteins·Shanteri SinghJon S Thorson
Nov 6, 2015·ACS Chemical Biology·Jing Zhang, Yujun George Zheng
May 5, 2016·ACS Combinatorial Science·Paula GarcíaRicardo L E Furlan
Jun 29, 2016·ACS Chemical Biology·Tyler D HuberJon S Thorson
Nov 2, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Steffen FriedrichFrank Hahn
Dec 13, 2016·Angewandte Chemie·Jochem DeenJohan Hofkens
Apr 7, 2017·Molecular BioSystems·J SheehanP Caffrey
Feb 1, 2017·Chembiochem : a European Journal of Chemical Biology·Kalli C CatcottZhaohui Sunny Zhou
Mar 5, 2015·Chemical Society Reviews·Sherif I ElshahawiJon S Thorson
Apr 1, 2006·Chembiochem : a European Journal of Chemical Biology·Changsheng ZhangJon S Thorson
Aug 7, 2018·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Tomoya HiranoHiroyuki Kagechika
Apr 16, 2016·F1000Research·Jason R KingGregory Stephanopoulos
Nov 15, 2018·Chembiochem : a European Journal of Chemical Biology·Sarah J HymbaughLindsay R Comstock
Mar 22, 2014·Chembiochem : a European Journal of Chemical Biology·Fang-Yuan Chang, Sean F Brady
May 14, 2020·Angewandte Chemie·Abigail J HerbertJason Micklefield
May 1, 2015·Chemical Science·Brian J C LawJason Micklefield
Jul 30, 2014·Journal of Natural Products·Wenjun ZhangChangsheng Zhang
Mar 15, 2011·ACS Combinatorial Science·Luciana MéndezRicardo L E Furlan
Jun 20, 2015·Journal of Natural Products·Khaled A ShaabanJon S Thorson

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.