Prostratin
Encyclopedia
Prostratin is a protein kinase C
activator found in the bark of the mamala tree of Samoa
, Homalanthus nutans (Euphorbiaceae
). While prostratin was originally isolated and identified as a new phorbol
from species of the genus Pimelea (Thymelaceae) in Australia
, the antiviral activity of prostratin was discovered during research on the traditional knowledge
of Samoan healers in Falealupo
village by ethnobotanist Paul Alan Cox
and a team at the U.S. National Cancer Institute. Samoan healers use the mamala tree to treat hepatitis. Research indicated that prostratin has potential to be useful in the treatment of HIV
as it could flush viral reservoirs in latently infected CD4+ T-cells.
. Pioneering agreements to protect indigenous intellectual property rights of the Samoan people were established between the Samoan government and the AIDS Research Alliance
, with 20% of ARA's profits to be returned to the Samoan people, and between the Samoan Government and the University of California, Berkeley
where a team led by Jay Keasling
is trying to isolate the gene sequence responsible for prostratin biosynthesis. Samoa
and UC Berkeley agreed to share equally in any commercial proceeds from the gene product.
In 2008, a team at Stanford University led by chemist Paul Wender has published an elegant four-step chemical synthesis
of prostratin from phorbol
. This practical synthesis produces gram quantities of prostratin, and is a major step forward in pharmaceutical development of prostratin.
In 2010, AIDS Research Alliance in Los Angeles, California announced that it signed a new licensing agreement with Stanford University, transferring exclusive rights of the technology developed by the Stanford research team.
Phase I human clinical trials of prostratin will be carried out by the AIDS ReSearch Alliance in Los Angeles, California.
Protein kinase C
Protein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...
activator found in the bark of the mamala tree of Samoa
Samoa
Samoa , officially the Independent State of Samoa, formerly known as Western Samoa is a country encompassing the western part of the Samoan Islands in the South Pacific Ocean. It became independent from New Zealand in 1962. The two main islands of Samoa are Upolu and one of the biggest islands in...
, Homalanthus nutans (Euphorbiaceae
Euphorbiaceae
Euphorbiaceae, the Spurge family are a large family of flowering plants with 300 genera and around 7,500 species. Most are herbs, but some, especially in the tropics, are also shrubs or trees. Some are succulent and resemble cacti....
). While prostratin was originally isolated and identified as a new phorbol
Phorbol
Phorbol is a natural, plant-derived organic compound. It is a member of the tigliane family of diterpenes. It was first isolated in 1934 as the hydrolysis product of croton oil, which is derived from the seeds of Croton tiglium. Phorbol's structure was determined in 1967...
from species of the genus Pimelea (Thymelaceae) in Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
, the antiviral activity of prostratin was discovered during research on the traditional knowledge
Traditional knowledge
Traditional knowledge , indigenous knowledge , traditional environmental knowledge and local knowledge generally refer to the long-standing traditions and practices of certain regional, indigenous, or local communities. Traditional knowledge also encompasses the wisdom, knowledge, and teachings...
of Samoan healers in Falealupo
Falealupo
Falealupo is a village in Samoa situated at the west end of Savai'i island from the dateline. The village has two main settlements, Falealupo-Uta, situated inland by the main island highway and Falealupo-Tai, situated by the sea...
village by ethnobotanist Paul Alan Cox
Paul Alan Cox
Dr. Paul Alan Cox is an ethnobotanist whose scientific research focuses on the ecology of island plants and the uses of plants by island peoples. After receiving his B.S. in Botany from Brigham Young University, he was awarded a Fulbright Fellowship to read for his M.Sc. in Ecology at the...
and a team at the U.S. National Cancer Institute. Samoan healers use the mamala tree to treat hepatitis. Research indicated that prostratin has potential to be useful in the treatment of HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
as it could flush viral reservoirs in latently infected CD4+ T-cells.
Overview
Prostratin is of interest because of its unique ability to activate latent viral reservoirs, while preventing healthy cells from infection, as well as its discovery through ethnobotanyEthnobotany
Ethnobotany is the scientific study of the relationships that exist between people and plants....
. Pioneering agreements to protect indigenous intellectual property rights of the Samoan people were established between the Samoan government and the AIDS Research Alliance
AIDS Research Alliance
AIDS Research Alliance of America is a national community-based non-profit medical research institution that seeks to develop a cure for HIV/AIDS, medical strategies to prevent new HIV infections and better treatments for people living with HIV/AIDS...
, with 20% of ARA's profits to be returned to the Samoan people, and between the Samoan Government and the University of California, Berkeley
University of California, Berkeley
The University of California, Berkeley , is a teaching and research university established in 1868 and located in Berkeley, California, USA...
where a team led by Jay Keasling
Jay Keasling
Dr. Jay D. Keasling is a Professor of Chemical and Biomolecular Engineering and Bioengineering at the University of California, Berkeley. He is also Associate Laboratory Director for Biosciences at the Lawrence Berkeley National Laboratory, the Founding Head of the Synthetic Biology Department in...
is trying to isolate the gene sequence responsible for prostratin biosynthesis. Samoa
Samoa
Samoa , officially the Independent State of Samoa, formerly known as Western Samoa is a country encompassing the western part of the Samoan Islands in the South Pacific Ocean. It became independent from New Zealand in 1962. The two main islands of Samoa are Upolu and one of the biggest islands in...
and UC Berkeley agreed to share equally in any commercial proceeds from the gene product.
In 2008, a team at Stanford University led by chemist Paul Wender has published an elegant four-step chemical synthesis
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...
of prostratin from phorbol
Phorbol
Phorbol is a natural, plant-derived organic compound. It is a member of the tigliane family of diterpenes. It was first isolated in 1934 as the hydrolysis product of croton oil, which is derived from the seeds of Croton tiglium. Phorbol's structure was determined in 1967...
. This practical synthesis produces gram quantities of prostratin, and is a major step forward in pharmaceutical development of prostratin.
In 2010, AIDS Research Alliance in Los Angeles, California announced that it signed a new licensing agreement with Stanford University, transferring exclusive rights of the technology developed by the Stanford research team.
Phase I human clinical trials of prostratin will be carried out by the AIDS ReSearch Alliance in Los Angeles, California.
External links
- AIDS Research Alliance
- Paul Wender and Stanford Prostratin synthesis
- Jay Keasling and Prostratin Genes
- Ethnobotanist Paul Cox
- Prostratin Agreements with Samoa
- NAIAD chemical database
- U.S. University Shares Drug Royalties with Samoa for Tree Gene
- Berkeley searches for AIDS cure in a Samoan indigenous tree
- Institute for Ethnomedicine
- National Tropical Botanical Garden
- Press Release-AIDS Research Alliance Gains Exclusive Rights To New Technology from Stanford University