Acetalins
Definition
Acetalins (acetyl plus enkephalin) are a class of opioid receptor ligands. They were opioid receptor antagonists determined through the use of Synthetic Peptide Combinatorial Libraries
Discovery
Dooley et al., in 1993 identified acetalins as a novel peptide antagonist to the mu receptor; through the use of combinatorial libraries. Deconvolution, or identification of individual compounds from the complex mixtures in the libraries, was achieved through an iterative process by using a positional scanning library1.
Structural Characteristics
Enkephalins are pentapeptide involved in regulating nociception in the body. They are endogenous ligands, or specifically endorphins, as they are internally derived and bind to the body's opioid receptors. Acetalins are acetyl plus enkephalin. The sequence of Acetalins is Ac-RFMWMK-NH2 1. Acetalin 1, Opioid Receptor Antagonist 1 sequence is Ac - Arg - Phe - Met - Trp - Met - Arg - NH2. Acetalin 2, Opioid Receptor Antagonist 2 sequence is Ac - Arg - Phe - Met - Trp - Met - Lys - NH2. Acetalin 3, Opioid Receptor Antagonist 3, Ac - Arg - Phe - Met - Trp - Met - Thr - NH2 1.
Mode of Action
Enkephalins families of opioid peptides are produced by the body. The receptors for enkephalin are the opioid receptors. These are G-protein-coupled receptors, with other opioids as ligands as well. The other endogenous opioids are dynorphins, endorphins, endomorphins, and nociceptin/orphanin FQ. Enkephalin inhibit ganglionic transmission by both pre- and post-synaptic actions in a mammalian parasympathetic ganglion 2. ORL1 receptors have a very high homology with the opioid receptors 3. Acetalins were found to bind poorly (.15,000 nM) to ORL1 in mu, delta and kappa opioid receptor assays 4. Acetalin 1 peptide has a high affinity for m (IC50 = 1.1 nM, Ki = 0.5nM) and k3 (IC50 = 2.6 nM, Ki = 1.4nM) opioid receptors. Acetalin 2 peptide has also a high affinity for m (IC50 = 1.9 nM, Ki = 0.4 nM) and k3 (IC50 = 0.7 nM, Ki = 0.4 nM) opioid receptors. Acetalin 3 peptide also shows a high affinity for m (IC50 = 1.7 nM, Ki = 0.8 nM) and k3 (IC50 = 1.0 nM, Ki = 0.6 nM) opioid receptors 1. Normally, acetalins can be assumed to control inhibitory mechanisms determining the rate of neurotransmitter release. If, however, opiates are administered with the intent of increasing the effects of these inhibitory mechanisms, then control will pass from the endogenous enkephalin to the exogenous opiates 5.
Functions
Affinity, acetalin ligands display a high affinity for m and k3 receptors, a weaker affinity for a receptors and no affinity for k2 receptors 6.
Mood and motivation, endorphins released from nerve endings of the central nervous system and the adrenal medulla act as analgesics and sedatives in the body and appear to affect mood and motivation.
An opium-based drug, brain releases endorphins and enkephalins. Enkephalins block pain signals in the spinal cord and these morphine-like substances whose functions are similar to those of opium-based drugs 6.
Natural pain killer, the naturally occurring opiates include enkephalins (methionine and leucine), endorphins (alpha, beta, gamma, and delta) and a growing number of synthetic (artificial) compounds are used as natural pain killer.
References
1.Dooley CT, Chung NN, Schiller PW, Houghten RA (1993). Acetalins:Opioid receptor antagonists determined through the use of synthetic peptide combinatorial libraries. PNAS., 90:10811-10815.
2.Katayama Y, Nishi S (1984). Sites and mechanisms of actions of enkephalin in the feline parasympathetic ganglion. J Physiol., 351:111-121.
3.Mollereau C, Parmentier M, Mailleux P, Butour JL, Moisand C, Chalon P, Caput D, Vassart G, Meunier JC (1994). ORL1, a novel member of the opioid receptor family: Cloning, functional expression and localization. FEBS Lett., 341:33-38.
4.Dooley CT, Spaeth CG, Berzetei-Gurske IP, Craymer K, Adapa ID, Brandt SR, Houghten RA, Toll L (1997). Binding and in vitro activities of peptides with high affinity for the nociceptin/orphanin FQ receptor, ORL1. J Pharmacol Exp Ther., 283(2):735-741.
5.Waterfield AA, Hughes J, Kosterlitz HW (1976). Cross tolerance between morphine and methionine-enkephalin. Nature, 260(5552):624-625.
6.8) Hughes MD, Zhang ZR, Sutherland AJ, Santos AF, Hine AV (2005). Discovery of active proteins directly from combinatorial randomized protein libraries without display, purification or sequencing: identification of novel zinc finger proteins. Nucleic Acids Res., 33(3):32.
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Acetalins (acetyl plus enkephalin) are a class of opioid receptor ligands. They were opioid receptor antagonists determined through the use of Synthetic Peptide Combinatorial Libraries
Discovery
Dooley et al., in 1993 identified acetalins as a novel peptide antagonist to the mu receptor; through the use of combinatorial libraries. Deconvolution, or identification of individual compounds from the complex mixtures in the libraries, was achieved through an iterative process by using a positional scanning library1.
Structural Characteristics
Enkephalins are pentapeptide involved in regulating nociception in the body. They are endogenous ligands, or specifically endorphins, as they are internally derived and bind to the body's opioid receptors. Acetalins are acetyl plus enkephalin. The sequence of Acetalins is Ac-RFMWMK-NH2 1. Acetalin 1, Opioid Receptor Antagonist 1 sequence is Ac - Arg - Phe - Met - Trp - Met - Arg - NH2. Acetalin 2, Opioid Receptor Antagonist 2 sequence is Ac - Arg - Phe - Met - Trp - Met - Lys - NH2. Acetalin 3, Opioid Receptor Antagonist 3, Ac - Arg - Phe - Met - Trp - Met - Thr - NH2 1.
Mode of Action
Enkephalins families of opioid peptides are produced by the body. The receptors for enkephalin are the opioid receptors. These are G-protein-coupled receptors, with other opioids as ligands as well. The other endogenous opioids are dynorphins, endorphins, endomorphins, and nociceptin/orphanin FQ. Enkephalin inhibit ganglionic transmission by both pre- and post-synaptic actions in a mammalian parasympathetic ganglion 2. ORL1 receptors have a very high homology with the opioid receptors 3. Acetalins were found to bind poorly (.15,000 nM) to ORL1 in mu, delta and kappa opioid receptor assays 4. Acetalin 1 peptide has a high affinity for m (IC50 = 1.1 nM, Ki = 0.5nM) and k3 (IC50 = 2.6 nM, Ki = 1.4nM) opioid receptors. Acetalin 2 peptide has also a high affinity for m (IC50 = 1.9 nM, Ki = 0.4 nM) and k3 (IC50 = 0.7 nM, Ki = 0.4 nM) opioid receptors. Acetalin 3 peptide also shows a high affinity for m (IC50 = 1.7 nM, Ki = 0.8 nM) and k3 (IC50 = 1.0 nM, Ki = 0.6 nM) opioid receptors 1. Normally, acetalins can be assumed to control inhibitory mechanisms determining the rate of neurotransmitter release. If, however, opiates are administered with the intent of increasing the effects of these inhibitory mechanisms, then control will pass from the endogenous enkephalin to the exogenous opiates 5.
Functions
Affinity, acetalin ligands display a high affinity for m and k3 receptors, a weaker affinity for a receptors and no affinity for k2 receptors 6.
Mood and motivation, endorphins released from nerve endings of the central nervous system and the adrenal medulla act as analgesics and sedatives in the body and appear to affect mood and motivation.
An opium-based drug, brain releases endorphins and enkephalins. Enkephalins block pain signals in the spinal cord and these morphine-like substances whose functions are similar to those of opium-based drugs 6.
Natural pain killer, the naturally occurring opiates include enkephalins (methionine and leucine), endorphins (alpha, beta, gamma, and delta) and a growing number of synthetic (artificial) compounds are used as natural pain killer.
References
1.Dooley CT, Chung NN, Schiller PW, Houghten RA (1993). Acetalins:Opioid receptor antagonists determined through the use of synthetic peptide combinatorial libraries. PNAS., 90:10811-10815.
2.Katayama Y, Nishi S (1984). Sites and mechanisms of actions of enkephalin in the feline parasympathetic ganglion. J Physiol., 351:111-121.
3.Mollereau C, Parmentier M, Mailleux P, Butour JL, Moisand C, Chalon P, Caput D, Vassart G, Meunier JC (1994). ORL1, a novel member of the opioid receptor family: Cloning, functional expression and localization. FEBS Lett., 341:33-38.
4.Dooley CT, Spaeth CG, Berzetei-Gurske IP, Craymer K, Adapa ID, Brandt SR, Houghten RA, Toll L (1997). Binding and in vitro activities of peptides with high affinity for the nociceptin/orphanin FQ receptor, ORL1. J Pharmacol Exp Ther., 283(2):735-741.
5.Waterfield AA, Hughes J, Kosterlitz HW (1976). Cross tolerance between morphine and methionine-enkephalin. Nature, 260(5552):624-625.
6.8) Hughes MD, Zhang ZR, Sutherland AJ, Santos AF, Hine AV (2005). Discovery of active proteins directly from combinatorial randomized protein libraries without display, purification or sequencing: identification of novel zinc finger proteins. Nucleic Acids Res., 33(3):32.
Please visit our Blog on Blogspot Bio-Synthesis
BIO-SYNTHESIS
BIO-SYNTHESIS, INC., is a leading life science products company with over 20 years of experience in the design and synthesis of Custom Peptide, small molecules and reagents for small scale research and bulk pharmaceutical trials. Using state of the art technology in our well-equipped laboratories.
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"The use of state-of-the art technology has allowed Bio-Synthesis, Inc. to rapidly gain recognition for its manufacturing quality & dependability of delivery."
Founded in 1984, Bio-Synthesis, Inc. was first known as OCS Laboratories. It was the first producer of commercially available synthetic DNA and, in 1985, became a producer of synthetic peptides. In 1989, OCS incorporated as Bio-Synthesis, Inc. and moved its laboratories to Lewisville, Texas. Today, BSI occupies 10,000 square feet of modern laboratory space (completed in 1995) located 20 miles from downtown Dallas and 10 miles from D/FW airport. Among the surrounding academic institutions are: University of Texas Southwestern Medical School (12 miles), University of North Texas (10 miles), and University of North Texas Health Science Center (25 miles). These universities provide excellent library resources. Since its inception, BSI has steadily expanded its product lines and services to meet the growing needs of the molecular biology community. It has maintained its position as an aggressive, innovative company in a highly competitive marketplace without sacrificing quality. In the beginning, our primary emphasis was on synthesizing high quality DNA primers and linkers, which were the initial uses of oligos. Today, newer technologies, such as gene construction, PCR, mutagenesis, combinatorial libraries, dye/adduct labeling, DNA microarrays, peptide-nucleic acid chimeras, etc. have challenged the molecular biology field. In response, BSI has branched into several related areas including DNA paternity testing, DNA HLA typing, PNA synthesis, genomic sequencing, fluorescence-based genotyping, custom organic synthesis and other molecular biology based applications.
The Research and Development Division comprises a number of Ph.D. and M.D. professionals with backgrounds in molecular biology, immunology, nucleic acids, peptide synthesis, general organic chemistry, and automated amino acid sequencing. The Molecular Biology Division is set up to handle most modern experimental procedures; the Immunology Division specializes in immunodiagnostic-based reagents.
Not only has BSI continued to provide quality DNA products and services for the research community, but it has also become a world leader in providing custom peptide products and services. Using state-of-the-art solid phase peptide chemistries, BSI provides high quality custom peptides, performs carrier conjugations, antipeptide antibody production, antigenic peptide design, synthesis of long and/or modified peptides, MALDI TOF analysis, contract research, consultation services and more.
Biomedical researchers worldwide in universities, biotech companies, private clinics, and government agencies use products from Bio-Synthesis, Inc. in studies ranging from PCR diagnostics to cancer research and the Human Genome Project. Contact us to discover how BSI can customize products/services to suit your research requirements.
For more detail please visit our About Us
Please Contact Us :
Address: 612 E. Main street
City: Lewisville
State: Texas
Country: USA
Postal Code: 75057
Phone Number: 972-420-8505
Founded in 1984, Bio-Synthesis, Inc. was first known as OCS Laboratories. It was the first producer of commercially available synthetic DNA and, in 1985, became a producer of synthetic peptides. In 1989, OCS incorporated as Bio-Synthesis, Inc. and moved its laboratories to Lewisville, Texas. Today, BSI occupies 10,000 square feet of modern laboratory space (completed in 1995) located 20 miles from downtown Dallas and 10 miles from D/FW airport. Among the surrounding academic institutions are: University of Texas Southwestern Medical School (12 miles), University of North Texas (10 miles), and University of North Texas Health Science Center (25 miles). These universities provide excellent library resources. Since its inception, BSI has steadily expanded its product lines and services to meet the growing needs of the molecular biology community. It has maintained its position as an aggressive, innovative company in a highly competitive marketplace without sacrificing quality. In the beginning, our primary emphasis was on synthesizing high quality DNA primers and linkers, which were the initial uses of oligos. Today, newer technologies, such as gene construction, PCR, mutagenesis, combinatorial libraries, dye/adduct labeling, DNA microarrays, peptide-nucleic acid chimeras, etc. have challenged the molecular biology field. In response, BSI has branched into several related areas including DNA paternity testing, DNA HLA typing, PNA synthesis, genomic sequencing, fluorescence-based genotyping, custom organic synthesis and other molecular biology based applications.
The Research and Development Division comprises a number of Ph.D. and M.D. professionals with backgrounds in molecular biology, immunology, nucleic acids, peptide synthesis, general organic chemistry, and automated amino acid sequencing. The Molecular Biology Division is set up to handle most modern experimental procedures; the Immunology Division specializes in immunodiagnostic-based reagents.
Not only has BSI continued to provide quality DNA products and services for the research community, but it has also become a world leader in providing custom peptide products and services. Using state-of-the-art solid phase peptide chemistries, BSI provides high quality custom peptides, performs carrier conjugations, antipeptide antibody production, antigenic peptide design, synthesis of long and/or modified peptides, MALDI TOF analysis, contract research, consultation services and more.
Biomedical researchers worldwide in universities, biotech companies, private clinics, and government agencies use products from Bio-Synthesis, Inc. in studies ranging from PCR diagnostics to cancer research and the Human Genome Project. Contact us to discover how BSI can customize products/services to suit your research requirements.
For more detail please visit our About Us
Please Contact Us :
Address: 612 E. Main street
City: Lewisville
State: Texas
Country: USA
Postal Code: 75057
Phone Number: 972-420-8505
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BIO-SYNTHESIS
BIO-SYNTHESIS, INC., is a leading life science products company with over 20 years of experience in the design and synthesis of Custom Peptide, small molecules and reagents for small scale research and bulk pharmaceutical trials. Using state of the art technology in our well-equipped laboratories.
Please visit our Blog on Blogspot Bio-Synthesis
Please visit our Blog on Blogspot Bio-Synthesis
Custom Antibody
As a leading supplier of genomic and proteomic research products, BSI is able to offer its customers integrated solutions for custom DNA synthesis, custom RNA synthesis, custom polyclonal antibody production, custom peptide synthesis, molecular diagnostic detection kits, DNA Real-Time PCR products, DNA microarray services and a wide range of custom DNA-based diagnostic kits and consumables.
The proteomic division is experienced in the design of peptides, both for antibody production and bioactive peptide synthesis, e.g cosmetic peptides. While the custom peptide synthesis division has the ability to produce thousands of modified or non-modified peptides per day for research applications, BSI also provides diagnostic/therapeutic GMP custom peptide production. Synthesis of custom peptides results in quantities ranging from milligrams to multi-kilograms. The staff in the custom antibody division provide expert support in the selection of peptide antigens for target antibody production and offer convenient custom-bundled packages with a wide range of host animals. In addition, peptide, antibody and protein arrays are also amongst its expertise.
BSI is a U.S. based company whose primary emphasis is on the synthesis of high quality custom products for a variety of applications and a full-service contract manufacturing organization (CMO) delivering research, development and production services for cGMP clinical batch manufacturing.
BIO-SYNTHESIS
BIO-SYNTHESIS, INC., is a leading life science products company with over 20 years of experience in the design and synthesis of Custom Peptide, small molecules and reagents for small scale research and bulk pharmaceutical trials. Using state of the art technology in our well-equipped laboratories.
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