TyrosineKinase Peptide3
Definition
The native peptide RRLIEDAEYAARG is derived from pp60src, and considered to be a generic substrate for various protein tyrosine kinases.
Discovery
Lou Q, et al., in 1995 determined the two amino acids -Ile-Tyr- were the two critical residues as a peptide substrate for p60c-src protein tyrosine kinase . Subsequently in 1996 they reported on the design and synthesis of a secondary 'one-bead, one-compound' combinatorial peptide library based on this dipeptide motif (XIYXXXX, where X = all 19 eukaryotic amino acids except for cysteine) 1. Normanno in 2003 analysed epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) 2.
Structural Characteristics
Sequence of Tyrosine Kinase Peptide 3 is, - Arg - Arg - Leu - Ile - Glu - Asp - Ala - Glu - pTyr - Ala - Ala - Arg - Gly - NH2. Lou Q. et al., in 1996 screened a secondary library for Tyrosine Kinase Peptide 3 for its ability to be phosphorylated by p60c-src PTK using [?32P] ATP as a tracer. Five of the strongest [32P]-labeled peptide-beads were identified and microsequenced: GIYWHHY, KIYDDYE, EIYEENG, EIYEEYE, and YIYEEED. A solid-phase phosphorylation assay was used to evaluate the structure-activity relationship of GIYWHHY. It was determined that Ile2, Tyr3, His5, and His6 were crucial for its activity as a substrate. Using various combinatorial peptide library approaches, Wu et al., 1997 and Schmitz et al., 1996 were successful in identifying some relatively potent peptide substrates for a number of PTKs. For example, YIYGSFK, GIYWHHY, and EEIYGEFF for Src PTK have Kms ranging between 25-55 M 3,4.
Mode of Action
PTKs are key enzymes in many signal transduction pathways and play a crucial role in many cell regulatory processes. It is estimated that there are over 2000 protein serine/threonine kinases and close to 100 different PTKs encoded by the human genome. Numerous small molecule inhibitors for various PTKs have been developed. PTKs play a crucial role in many cell regulatory processes such as mitogenesis, differentiation and development, oncogenesis, angiogenesis, cell survival and apoptosis, cell shape and adhesion, cell cycle control, growth control, T-cell and B-cell activation, responses to extracellular stimuli, neurotransmitter signaling, platelet activation, transcription control, and glucose uptake 4. Synthetic peptides derived from autophosphorylation sites or phosphorylation sites of protein substrates are often poor substrates for PTK. They can serve as important reagents to study the mechanism of action of the enzyme, to map the pharmacophores of the substrate binding pocket, and to be used as leads for the design of peptidomimetic inhibitors. The native peptide derived from pp60src, and considered to be a generic substrate for various protein tyrosine kinases. The fluorescent and biotinylated peptides are used to design a variety of assays for PTKs.
The epidermal growth factor receptor (EGFR) has been identified as a relevant target as it is involved in regulating several cellular functions important in the proliferation and survival of cancer cells, is commonly expressed at high levels in a range of tumors, and high expression is often related to poor prognosis. EGFR is a member of the ErbB family of receptors which also includes ErbB-2, ErbB-3, and ErbB-4. These receptors form dimers of the same type (homodimers) or with other family members (heterodimers), each combination resulting in different downstream effects. Some of the most advanced targeted agents in development are the EGFR tyrosine kinase inhibitors (EGFR-TKIs), of which ZD1839 ('Iressa') is an example. Tyrosine kinase inhibitors affect EGFR signaling and may also affect signaling of other ErbB family members 2.
Functions
Cell signaling, PTKs (as well as serine and threonine kinases) are crucial enzymes in many cell signalling pathways and are altered or overexpressed in many disease states. Inhibitors against some of these enzymes may be useful for the treatment of a number of diseases.
Assays for PTKs, the fluorescent and biotinylated peptides are used to design a variety of assays for PTKs 1.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs): EGFR-TKIs have been shown in preclinical studies to increase the efficacy of cytotoxic drugs and Phase III trials of such combinations are ongoing. On the basis that different signal transduction pathways contribute to the control of tumor growth, future therapeutic approaches are likely to involve combination of different targeted agents 3.
References
1.Lou Q, Leftwich ME, Lam KS (1995). Identification of GIYWHHY as a novel peptide substrate for human p60c-src protein tyrosine kinase. Bioorganic & Medicinal Chemistry., 4(5):677:682.
2.Normanno N, Maiello MR, De Luca A (2003). Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs): simple drugs with a complex mechanism of action. J Cell Physiol., 194(1):13-9.
3.Hunter T (1997). Oncoprotein networks. Cell, 88:333-346.
4.Wu JJ, Phan H and Lam KS (1998). Bioorg. Med. Chem. Lett., 8:2279-2284.
5.Schmitz R, Baumann G and Gram H (1996). J. Mol. Biol., 260:664-677.
For more detail please visit here TyrosineKinase Peptide3
The native peptide RRLIEDAEYAARG is derived from pp60src, and considered to be a generic substrate for various protein tyrosine kinases.
Discovery
Lou Q, et al., in 1995 determined the two amino acids -Ile-Tyr- were the two critical residues as a peptide substrate for p60c-src protein tyrosine kinase . Subsequently in 1996 they reported on the design and synthesis of a secondary 'one-bead, one-compound' combinatorial peptide library based on this dipeptide motif (XIYXXXX, where X = all 19 eukaryotic amino acids except for cysteine) 1. Normanno in 2003 analysed epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) 2.
Structural Characteristics
Sequence of Tyrosine Kinase Peptide 3 is, - Arg - Arg - Leu - Ile - Glu - Asp - Ala - Glu - pTyr - Ala - Ala - Arg - Gly - NH2. Lou Q. et al., in 1996 screened a secondary library for Tyrosine Kinase Peptide 3 for its ability to be phosphorylated by p60c-src PTK using [?32P] ATP as a tracer. Five of the strongest [32P]-labeled peptide-beads were identified and microsequenced: GIYWHHY, KIYDDYE, EIYEENG, EIYEEYE, and YIYEEED. A solid-phase phosphorylation assay was used to evaluate the structure-activity relationship of GIYWHHY. It was determined that Ile2, Tyr3, His5, and His6 were crucial for its activity as a substrate. Using various combinatorial peptide library approaches, Wu et al., 1997 and Schmitz et al., 1996 were successful in identifying some relatively potent peptide substrates for a number of PTKs. For example, YIYGSFK, GIYWHHY, and EEIYGEFF for Src PTK have Kms ranging between 25-55 M 3,4.
Mode of Action
PTKs are key enzymes in many signal transduction pathways and play a crucial role in many cell regulatory processes. It is estimated that there are over 2000 protein serine/threonine kinases and close to 100 different PTKs encoded by the human genome. Numerous small molecule inhibitors for various PTKs have been developed. PTKs play a crucial role in many cell regulatory processes such as mitogenesis, differentiation and development, oncogenesis, angiogenesis, cell survival and apoptosis, cell shape and adhesion, cell cycle control, growth control, T-cell and B-cell activation, responses to extracellular stimuli, neurotransmitter signaling, platelet activation, transcription control, and glucose uptake 4. Synthetic peptides derived from autophosphorylation sites or phosphorylation sites of protein substrates are often poor substrates for PTK. They can serve as important reagents to study the mechanism of action of the enzyme, to map the pharmacophores of the substrate binding pocket, and to be used as leads for the design of peptidomimetic inhibitors. The native peptide derived from pp60src, and considered to be a generic substrate for various protein tyrosine kinases. The fluorescent and biotinylated peptides are used to design a variety of assays for PTKs.
The epidermal growth factor receptor (EGFR) has been identified as a relevant target as it is involved in regulating several cellular functions important in the proliferation and survival of cancer cells, is commonly expressed at high levels in a range of tumors, and high expression is often related to poor prognosis. EGFR is a member of the ErbB family of receptors which also includes ErbB-2, ErbB-3, and ErbB-4. These receptors form dimers of the same type (homodimers) or with other family members (heterodimers), each combination resulting in different downstream effects. Some of the most advanced targeted agents in development are the EGFR tyrosine kinase inhibitors (EGFR-TKIs), of which ZD1839 ('Iressa') is an example. Tyrosine kinase inhibitors affect EGFR signaling and may also affect signaling of other ErbB family members 2.
Functions
Cell signaling, PTKs (as well as serine and threonine kinases) are crucial enzymes in many cell signalling pathways and are altered or overexpressed in many disease states. Inhibitors against some of these enzymes may be useful for the treatment of a number of diseases.
Assays for PTKs, the fluorescent and biotinylated peptides are used to design a variety of assays for PTKs 1.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs): EGFR-TKIs have been shown in preclinical studies to increase the efficacy of cytotoxic drugs and Phase III trials of such combinations are ongoing. On the basis that different signal transduction pathways contribute to the control of tumor growth, future therapeutic approaches are likely to involve combination of different targeted agents 3.
References
1.Lou Q, Leftwich ME, Lam KS (1995). Identification of GIYWHHY as a novel peptide substrate for human p60c-src protein tyrosine kinase. Bioorganic & Medicinal Chemistry., 4(5):677:682.
2.Normanno N, Maiello MR, De Luca A (2003). Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs): simple drugs with a complex mechanism of action. J Cell Physiol., 194(1):13-9.
3.Hunter T (1997). Oncoprotein networks. Cell, 88:333-346.
4.Wu JJ, Phan H and Lam KS (1998). Bioorg. Med. Chem. Lett., 8:2279-2284.
5.Schmitz R, Baumann G and Gram H (1996). J. Mol. Biol., 260:664-677.
For more detail please visit here TyrosineKinase Peptide3
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
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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
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 alaboratories.
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