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Science Gifts 2014: Books on Drug Discovery and Medicinal Chemistry - Corante

Science Gifts 2014: Books on Drug Discovery and Medicinal Chemistry - Corante | Marine Natural Products | Scoop.it
Science Gifts 2014: Books on Drug Discovery and Medicinal Chemistry
Corante
Today I wanted to highlight books specifically on medicinal chemistry and drug discovery. Those are always festive additions to the holiday season, right?
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Drug Discovery of Inflammation through Complement receptors: Molecular Modeling of Human Complement Protein Receptors for the Drug Discovery of Inflammation

Drug Discovery of Inflammation through Complement receptors: Molecular Modeling of Human Complement Protein Receptors for the Drug Discovery of Inflammation | Marine Natural Products | Scoop.it
Drug Discovery of Inflammation through Complement receptors: Molecular Modeling of Human Complement Protein Receptors for the Drug Discovery of Inflammation Offer Price $62.10 ISBN:3639333462 Authors Madhu Babu Battu List Price : $69.00 Availablity...
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NRPquest: Coupling Mass Spectrometry and Genome Mining for Nonribosomal Peptide Discovery

NRPquest: Coupling Mass Spectrometry and Genome Mining for Nonribosomal Peptide Discovery | Marine Natural Products | Scoop.it

Nonribosomal peptides (NRPs) such as vancomycin and daptomycin are among the most effective antibiotics. While NRPs are biomedically important, the computational techniques for sequencing these peptides are still in their infancy. The recent emergence of mass spectrometry techniques for NRP analysis (capable of sequencing an NRP from small amounts of nonpurified material) revealed an enormous diversity of NRPs. However, as many NRPs have nonlinear structure (e.g., cyclic or branched-cyclic peptides), the standard de novo sequencing tools (developed for linear peptides) are not applicable to NRP analysis. Here, we introduce the first NRP identification algorithm, NRPquest, that performs mutation-tolerant and modification-tolerant searches of spectral data sets against a database of putative NRPs. In contrast to previous studies aimed at NRP discovery (that usually report very few NRPs), NRPquest revealed nearly a hundred NRPs (including unknown variants of previously known peptides) in a single study. This result indicates that NRPquest can potentially make MS-based NRP identification as robust as the identification of linear peptides in traditional proteomics.

 

Hosein Mohimani†, Wei-Ting Liu‡, Roland D. Kersten§, Bradley S. Moore§, Pieter C. Dorrestein‡, and Pavel A. Pevzner
J. Nat. Prod., Article ASAPDOI: 10.1021/np500370cPublication Date (Web): August 12, 2014

 


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Belizentrin, a Highly Bioactive Macrocycle from the Dinoflagellate Prorocentrum belizeanum

Belizentrin, a Highly Bioactive Macrocycle from the Dinoflagellate Prorocentrum belizeanum | Marine Natural Products | Scoop.it

Belizentrin (1), a novel 25-membered polyketide-derived macrocycle, was isolated from cultures of the marine dinoflagellate Prorocentrum belizeanum. This metabolite is the first member of an unprecedented class of polyunsaturated and polyhydroxylated macrolactams. The structure of 1 was primarily determined by NMR and computational methods. Pharmacological assays with cerebellar cells showed that 1 produces important changes in neuronal network integrity at nanomolar concentrations.

 

Humberto J. Domínguez†, José G. Napolitano†, M. Teresa Fernández-Sánchez‡, David Cabrera-García‡, Antonello Novelli§, Manuel Norte†, José J. Fernández*†, and Antonio Hernández DaranasOrg. Lett., Article ASAPDOI: 10.1021/ol502102f


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NRPquest: Coupling Mass Spectrometry and Genome Mining for Nonribosomal Peptide Discovery

NRPquest: Coupling Mass Spectrometry and Genome Mining for Nonribosomal Peptide Discovery | Marine Natural Products | Scoop.it

Nonribosomal peptides (NRPs) such as vancomycin and daptomycin are among the most effective antibiotics. While NRPs are biomedically important, the computational techniques for sequencing these peptides are still in their infancy. The recent emergence of mass spectrometry techniques for NRP analysis (capable of sequencing an NRP from small amounts of nonpurified material) revealed an enormous diversity of NRPs. However, as many NRPs have nonlinear structure (e.g., cyclic or branched-cyclic peptides), the standard de novo sequencing tools (developed for linear peptides) are not applicable to NRP analysis. Here, we introduce the first NRP identification algorithm, NRPquest, that performs mutation-tolerant and modification-tolerant searches of spectral data sets against a database of putative NRPs. In contrast to previous studies aimed at NRP discovery (that usually report very few NRPs), NRPquest revealed nearly a hundred NRPs (including unknown variants of previously known peptides) in a single study. This result indicates that NRPquest can potentially make MS-based NRP identification as robust as the identification of linear peptides in traditional proteomics.

 

Hosein Mohimani†, Wei-Ting Liu‡, Roland D. Kersten§, Bradley S. Moore§, Pieter C. Dorrestein‡, and Pavel A. Pevzner
J. Nat. Prod., Article ASAPDOI: 10.1021/np500370cPublication Date (Web): August 12, 2014

 


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Site-Specific Integration of Amino Acid Fragments into Cyclic Peptides - Journal of the American Chemical Society (ACS Publications)

Site-Specific Integration of Amino Acid Fragments into Cyclic Peptides - Journal of the American Chemical Society (ACS Publications) | Marine Natural Products | Scoop.it
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Natural products as starting points for the synthesis of complex and diverse compounds

Natural products as starting points for the synthesis of complex and diverse compounds | Marine Natural Products | Scoop.it

Natural products and their derivatives are used as treatments for numerous diseases. Many of these compounds are structurally complex, possessing a high percentage of sp3 hybridized carbons and multiple stereogenic centers. Due to the difficulties associated with the isolation of large numbers of novel natural products, lead discovery efforts over the last two decades have shifted toward the screening of less structurally complex synthetic compounds. While there have been many success stories from these campaigns, the modulation of certain biological targets (e.g. protein–protein interactions) and disease areas (e.g. antibacterials) often require complex molecules. Thus, there is considerable interest in the development of strategies to construct large collections of compounds that mimic the complexity of natural products. Several of these strategies focus on the conversion of simple starting materials to value-added products and have been reviewed elsewhere. Herein we review the use of natural products as starting points for the generation of complex compounds, discussing both early ad hoc efforts and a more recent systematization of this approach.

 

Karen C. Morrisona and   Paul J. Hergenrother Show AffiliationsNat. Prod. Rep., 2014, Advance Article


DOI: 10.1039/C3NP70063A


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Industrial natural product chemistry for drug discovery and development

Industrial natural product chemistry for drug discovery and development | Marine Natural Products | Scoop.it

In addition to their prominent role in basic biological and chemical research, natural products are a rich source of commercial products for the pharmaceutical and other industries. Industrial natural product chemistry is of fundamental importance for successful product development, as the vast majority (ca. 80%) of commercial drugs derived from natural products require synthetic efforts, either to enable economical access to bulk material, and/or to optimize drug properties through structural modifications. This review aims to illustrate issues on the pathway from lead to product, and how they have been successfully addressed by modern natural product chemistry. It is focused on natural products of current relevance that are, or are intended to be, used as pharmaceuticals.

 

Armin Bauer*a and   Mark Brö Nat. Prod. Rep., 2014, Advance Article


DOI: 10.1039/C3NP70058E


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Simplifying Proton NMR Spectra by Instant Homonuclear Broadband Decoupling

Simplifying Proton NMR Spectra by Instant Homonuclear Broadband Decoupling | Marine Natural Products | Scoop.it

Shift work: The new NMR technique, instant homonuclear decoupling, which is achieved by slice-selective homo-decoupling during acquisition, yields pure-shift NMR spectra (see picture) which can be recorded like regular 1D spectra. No special data processing is necessary and this approach can also be easily adapted for the direct dimension of two- and multidimensional spectra, giving improved resolution.

 

Dr. N. Helge Meyer,Prof. Klaus Zangger*Angewandte Chemie International Edition

Article first published online: 3 JUN 2013

DOI: 10.1002/anie.201300129


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NatProdChem's curator insight, June 4, 2013 6:52 AM

Will shurely be usefull for 2D of scarce natural products.

 

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RNA Editing and Drug Discovery for Cancer Therapy

RNA Editing and Drug Discovery for Cancer Therapy | Marine Natural Products | Scoop.it
The Scientific World Journal is a peer-reviewed, open access journal covering a wide range of subjects in science, technology, and medicine.
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NMR of a Mass Spec Species - Corante

NMR of a Mass Spec Species - Corante | Marine Natural Products | Scoop.it
NMR of a Mass Spec Species
Corante
I have to say, I didn't even know that this could be done. This paper from Angewandte Chemie describes a mass spec/NMR combination analysis that had never occurred to me as possible.
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Spatial and temporal control of fungal natural product synthesis

Spatial and temporal control of fungal natural product synthesis | Marine Natural Products | Scoop.it

Despite their oftentimes-elusive ecological role, fungal natural products have, for better or worse, impacted our daily lives tremendously owing to their diverse and potent bioactive properties. This Janus-faced nature of fungal natural products inevitably ushered in a field of research dedicated towards understanding the ecology, organisms, genes, enzymes, and biosynthetic pathways that give rise to this arsenal of diverse and complex chemistry. Ongoing research in fungal secondary metabolism has not only increased our appreciation for fungal natural products as an asset but also sheds light on the pivotal role that these once-regarded “metabolic wastes” play in fungal biology, defense, and stress response in addition to their potential contributions towards human mycoses. Full orchestration of secondary metabolism requires not only the seamless coordination between temporal and spatial control of SM-associated machineries (e.g. enzymes, cofactors, intermediates, and end-products) but also integration of these machineries into primary metabolic processes and established cellular mechanisms. An intriguing, but little known aspect of microbial natural product synthesis lies in the spatial organization of both pathway intermediates and enzymes responsible for the production of these compounds. In this highlight, we summarize some major breakthroughs in understanding the genes and regulation of fungal natural product synthesis and introduce the current state of knowledge on the spatial and temporal control of fungal natural product synthesis.

 

Fang Yun Lim and   Nancy P. Keller
Nat. Prod. Rep., 2014, Advance Article
DOI: 10.1039/C4NP00083H
Published 21 Aug 2014


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Belizentrin, a Highly Bioactive Macrocycle from the Dinoflagellate Prorocentrum belizeanum

Belizentrin, a Highly Bioactive Macrocycle from the Dinoflagellate Prorocentrum belizeanum | Marine Natural Products | Scoop.it

Belizentrin (1), a novel 25-membered polyketide-derived macrocycle, was isolated from cultures of the marine dinoflagellate Prorocentrum belizeanum. This metabolite is the first member of an unprecedented class of polyunsaturated and polyhydroxylated macrolactams. The structure of 1 was primarily determined by NMR and computational methods. Pharmacological assays with cerebellar cells showed that 1 produces important changes in neuronal network integrity at nanomolar concentrations.

 

Humberto J. Domínguez†, José G. Napolitano†, M. Teresa Fernández-Sánchez‡, David Cabrera-García‡, Antonello Novelli§, Manuel Norte†, José J. Fernández*†, and Antonio Hernández DaranasOrg. Lett., Article ASAPDOI: 10.1021/ol502102f
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Spatial and temporal control of fungal natural product synthesis

Spatial and temporal control of fungal natural product synthesis | Marine Natural Products | Scoop.it

Despite their oftentimes-elusive ecological role, fungal natural products have, for better or worse, impacted our daily lives tremendously owing to their diverse and potent bioactive properties. This Janus-faced nature of fungal natural products inevitably ushered in a field of research dedicated towards understanding the ecology, organisms, genes, enzymes, and biosynthetic pathways that give rise to this arsenal of diverse and complex chemistry. Ongoing research in fungal secondary metabolism has not only increased our appreciation for fungal natural products as an asset but also sheds light on the pivotal role that these once-regarded “metabolic wastes” play in fungal biology, defense, and stress response in addition to their potential contributions towards human mycoses. Full orchestration of secondary metabolism requires not only the seamless coordination between temporal and spatial control of SM-associated machineries (e.g. enzymes, cofactors, intermediates, and end-products) but also integration of these machineries into primary metabolic processes and established cellular mechanisms. An intriguing, but little known aspect of microbial natural product synthesis lies in the spatial organization of both pathway intermediates and enzymes responsible for the production of these compounds. In this highlight, we summarize some major breakthroughs in understanding the genes and regulation of fungal natural product synthesis and introduce the current state of knowledge on the spatial and temporal control of fungal natural product synthesis.

 

Fang Yun Lim and   Nancy P. Keller
Nat. Prod. Rep., 2014, Advance Article
DOI: 10.1039/C4NP00083H
Published 21 Aug 2014


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Density Functional Theory Calculations in Stereochemical Determination of Terpecurcumins J–W, Cytotoxic Terpene-Conjugated Curcuminoids from Curcuma longa L.

Density Functional Theory Calculations in Stereochemical Determination of Terpecurcumins J–W, Cytotoxic Terpene-Conjugated Curcuminoids from Curcuma longa L. | Marine Natural Products | Scoop.it

Fourteen novel terpene-conjugated curcuminoids, terpecurcumins J–W (1–14), have been isolated from the rhizomes of Curcuma longa L. Among them, terpecurcumins J–Q and V represent four unprecedented skeletons featuring an unusual core of hydrobenzannulated[6,6]-spiroketal (1 and 2), bicyclo[2.2.2]octene (3–7), bicyclo[3.1.3]octene (8), and spiroepoxide (13), respectively. The structures of compounds 1–14 were elucidated by extensive spectroscopic analysis, and their absolute configurations were established by electronic circular dichroism, vibrational circular dichroism, and 13C NMR spectroscopic data analysis, together with density functional theory calculations. The structure and configuration of 1 was further confirmed by single-crystal X-ray diffraction (Cu Kα). The biogenetic pathways of 1–14 were proposed, involving Michael addition, condensation, Diels–Alder cycloaddition, and electrophilic substitution reactions. Terpecurcumins showed more potent cytotoxic activities than curcumin and ar-/β-turmerone. Among them, terpecurcumin Q (8) exhibited IC50 of 3.9 μM against MCF-7 human breast cancer cells, and mitochondria-mediated apoptosis played an important role in the overall growth inhibition. Finally, LC/MS/MS quantitative analysis of five representative terpecurcumins indicated these novel compounds were present in C. longa at parts per million level.

 

 

Xionghao Lin†, Shuai Ji†, Xue Qiao†, Hongbo Hu‡, Ni Chen‡, Yinhui Dong‡, Yun Huang†, Dean Guo†, Pengfei Tu†, and Min YeJ. Org. Chem., Article ASAPDOI: 10.1021/jo401859uPublication Date (Web): November 12, 2013

 


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Mass spectrometry and NMR spectroscopy: modern high-end detectors for high resolution separation techniques – state of the art in natural product HPLC-MS, HPLC-NMR, and CE-MS hyphenations

Mass spectrometry and NMR spectroscopy: modern high-end detectors for high resolution separation techniques – state of the art in natural product HPLC-MS, HPLC-NMR, and CE-MS hyphenations | Marine Natural Products | Scoop.it

Current natural product research is unthinkable without the use of high resolution separation techniques as high performance liquid chromatography or capillary electrophoresis (HPLC or CE respectively) combined with mass spectrometers (MS) or nuclear magnetic resonance (NMR) spectrometers. These hyphenated instrumental analysis platforms (CE-MS, HPLC-MS or HPLC-NMR) are valuable tools for natural product de novo identification, as well as the authentication, distribution, and quantification of constituents in biogenic raw materials, natural medicines and biological materials obtained from model organisms, animals and humans. Moreover, metabolic profiling and metabolic fingerprinting applications can be addressed as well as pharmacodynamic and pharmacokinetic issues. This review provides an overview of latest technological developments, discusses the assets and drawbacks of the available hyphenation techniques, and describes typical analytical workflows.

 

Christoph Seger,ab   Sonja Sturma and   Hermann Stuppner
Nat. Prod. Rep., 2013, Advance Article


DOI: 10.1039/C3NP70015A


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A Common Origin for Guanidinobutanoate Starter Units in Antifungal Natural Products

A Common Origin for Guanidinobutanoate Starter Units in Antifungal Natural Products | Marine Natural Products | Scoop.it

Keeping it basic: Arginine provides the exotic 4-guanidinobutanoate starter unit for two different types of zwitterionic polyketide (an example for one type is shown in the picture) produced by the same Streptomyces bacterium. The three-step precursor pathway is initiated by a remarkable decarboxylating monooxygenase with high specificity for arginine.

 

Dr. Hui Hong1,*,Taicia Fill2,Prof. Peter F. Leadlay

 

Angewandte Chemie International Edition

 

Article first published online: 11 NOV 2013

DOI: 10.1002/anie.201308136


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Access : Quantitative molecular networking to profile marine cyanobacterial metabolomes

Access : Quantitative molecular networking to profile marine cyanobacterial metabolomes | Marine Natural Products | Scoop.it

Untargeted liquid chromatography-MS (LC-MS) is used to rapidly profile crude natural product (NP) extracts; however, the quantity of data produced can become difficult to manage. Molecular networking based on MS/MS data visualizes these complex data sets to aid their initial interpretation. Here, we developed an additional visualization step for the molecular networking workflow to provide relative and absolute quantitation of a specific compound in an extract. The new visualization also facilitates combination of several metabolomes into one network, and so was applied to an MS/MS data set from 20 crude extracts of cultured marine cyanobacteria. The resultant network illustrates the high chemical diversity present among marine cyanobacteria. It is also a powerful tool for locating producers of specific metabolites. In order to dereplicate and identify culture-based sources of known compounds, we added MS/MS data from 60 pure NPs and NP analogs to the 20-strain network. This dereplicated six metabolites directly and offered structural information on up to 30 more. Most notably, our visualization technique allowed us to identify and quantitatively compare several producers of the bioactive and biosynthetically intriguing lipopeptide malyngamide C. Our most prolific producer, a Panamanian strain of Okeania hirsuta (PAB10FEB10-01), was found to produce at least 0.024 mg of malyngamide C per mg biomass (2.4%, w/dw) and is now undergoing genome sequencing to access the corresponding biosynthetic machinery.

 

 

The Journal of Antibiotics , (27 November 2013) | doi:10.1038/ja.2013.120

Quantitative molecular networking to profile marine cyanobacterial metabolomes

Jacob R Winnikoff, Evgenia Glukhov, Jeramie Watrous, Pieter C Dorrestein and William H Gerwick

 

 

 


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