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Integrating Chemical and Biological Profiling for the Functional Annotation of Complex Natural Product Mixtures

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Air date: Monday, June 12, 2017, 10:00:00 AM
Time displayed is Eastern Time, Washington DC Local
Views: Total views: 142, (81 Live, 61 On-demand)
Category: National Center for Complementary and Integrative Health
Runtime: 01:02:53
Description: The National Center for Complementary and Integrative Health (NCCIH) presents the integrative Medicine Research Lecture Series. The series provides overviews of the current state of research and practice involving complementary health approaches and explores perspectives on the emerging discipline of integrative medicine.

It is challenging to identify the active components within complex mixtures of natural products and understand their modes of action. Thanks to recent technological developments in analytical chemistry and high-content screening, researchers have new opportunities to address tough questions posed by natural product profiling.

Dr. Linington’s laboratory is developing new methods for the unbiased chemical characterization of natural product mixtures as part of a collaborative program funded by the National Center for Complementary and Integrative Health and the Office of Dietary Supplements. They are also creating new informatics tools to relate the presence or absence of specific metabolites to observations of biological phenotypes in profiling assays. Together, these systems are providing a broad perspective on the biological roles of all metabolites in complex samples.

During this lecture, Dr. Linington will share his perspective on potential solutions for the unbiased chemical characterization of complex natural product mixtures, discuss the advantages of high-content assay systems for target-agnostic biological profiling, and highlight opportunities provided by the integration of orthogonal datasets for the functional characterization of natural product samples.

Dr. Linington is part of a new generation of natural products researchers invested in the biological attributes of natural products leads. He explores the general areas of natural product drug development and the exploration of natural products as chemical genetic tools. His research program has focused heavily on the development of new multiparametric screening tools for the early prediction of compound modes of action from primary screening data, and the development of new, more efficient compound isolation and structure elucidation methods.

Early in his academic career, Dr. Linington’s research focused on the discovery of novel bioactive molecules from natural sources as lead compounds for drug development. The targets of these drug discovery efforts included pathogenic bacteria, cancer cell lines, and global health diseases, with a particular focus on protozoan parasites. This work led to the identification of a number of important molecules that have been studied by his group and others in the years since their discovery. Examples of these discoveries include the identification of gallinamide A from a Panamanian marine cyanobacterium, which displays very potent and selective activity against Plasmodium falciparum (the parasite that causes malaria), and which has recently been shown to function by inhibition of falcipain and cathepsin L, both at nanomolar concentrations. More recently, his group has discovered the lobosamide class of polyketides, which are potent lead compounds with large windows of efficacy against T. brucei, and used genome-guided discovery tools to identify other compound in this class from different producing organisms. His work in this area has included a strong emphasis on kinetoplastid parasites, and has resulted in numerous publications describing the discovery, medicinal chemistry optimization, and target identification for a variety of different compound classes.

For more information go to https://nccih.nih.gov/news/events/IMlectures
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NLM Title: Integrating chemical and biological profiling for the functional annotation of complex natural product mixtures / Roger Linington.
Author: Linington, Roger.
National Institutes of Health (U.S.),
Publisher:
Abstract: (CIT): The National Center for Complementary and Integrative Health (NCCIH) presents the integrative Medicine Research Lecture Series. The series provides overviews of the current state of research and practice involving complementary health approaches and explores perspectives on the emerging discipline of integrative medicine. It is challenging to identify the active components within complex mixtures of natural products and understand their modes of action. Thanks to recent technological developments in analytical chemistry and high-content screening, researchers have new opportunities to address tough questions posed by natural product profiling. Dr. Linington's laboratory is developing new methods for the unbiased chemical characterization of natural product mixtures as part of a collaborative program funded by the National Center for Complementary and Integrative Health and the Office of Dietary Supplements. They are also creating new informatics tools to relate the presence or absence of specific metabolites to observations of biological phenotypes in profiling assays. Together, these systems are providing a broad perspective on the biological roles of all metabolites in complex samples. During this lecture, Dr. Linington will share his perspective on potential solutions for the unbiased chemical characterization of complex natural product mixtures, discuss the advantages of high-content assay systems for target-agnostic biological profiling, and highlight opportunities provided by the integration of orthogonal datasets for the functional characterization of natural product samples. Dr. Linington is part of a new generation of natural products researchers invested in the biological attributes of natural products leads. He explores the general areas of natural product drug development and the exploration of natural products as chemical genetic tools. His research program has focused heavily on the development of new multiparametric screening tools for the early prediction of compound modes of action from primary screening data, and the development of new, more efficient compound isolation and structure elucidation methods. Early in his academic career, Dr. Linington's research focused on the discovery of novel bioactive molecules from natural sources as lead compounds for drug development. The targets of these drug discovery efforts included pathogenic bacteria, cancer cell lines, and global health diseases, with a particular focus on protozoan parasites. This work led to the identification of a number of important molecules that have been studied by his group and others in the years since their discovery. Examples of these discoveries include the identification of gallinamide A from a Panamanian marine cyanobacterium, which displays very potent and selective activity against Plasmodium falciparum (the parasite that causes malaria), and which has recently been shown to function by inhibition of falcipain and cathepsin L, both at nanomolar concentrations. More recently, his group has discovered the lobosamide class of polyketides, which are potent lead compounds with large windows of efficacy against T. brucei, and used genome-guided discovery tools to identify other compound in this class from different producing organisms. His work in this area has included a strong emphasis on kinetoplastid parasites, and has resulted in numerous publications describing the discovery, medicinal chemistry optimization, and target identification for a variety of different compound classes.
Subjects: Biological Products--chemistry
Publication Types: Lectures
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NLM Classification: QV 241
NLM ID: 101708392
CIT Live ID: 23431
Permanent link: https://videocast.nih.gov/launch.asp?23349