Custom Peptide Synthesis Publications

Overview

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The depth of our peptide synthesis capabilities are best demonstrated by our customers' publications that cite our services. Since 2004, GenScript's Custom Peptide Services have helped thousands of scientists publish their research in peer-reviewed journals like Science, Nature, Cell, and PNAS. Currently, over 2400 publications cite our peptide synthesis services. Below, read the synopses and view some of the hottest publications that have recently cited GenScript peptide synthesis services. Visit this page again soon for new publication postings.

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Cancer
Diabetes
Immunology
Vaccine Development

Vaccine Development

• New Hepatitis B DNA vaccine

  In this study a new Hepatitis B virus (HBV) DNA vaccine capable of eliciting both humoral and cell-mediated immune responses was developed in an effort to combat the 600,000 annual new cases of HBV, which are added to the 370 million people already suffering from chronic infection. HBV infects human liver cells, leading to cirrhosis of the liver and eventually hepatocellular carcinoma. Read more>> The vaccine was designed to include plasmids expressing sequences from the major surface protein, major S as well as plasmids expressing a synthetic consensus HBV core antigen. When the plasmids were combined to form a multivalent cocktail vaccine, they were capable of stimulating strong immune responses in monkeys and mice.

  DNA vaccine cocktail expressing genotype A and C HBV surface and consensus core antigens generates robust cytotoxic and antibody responses in mice and Rhesus macaques. Obeng-Adjei, N et al. (2013) Cancer Gene Therapy. 20: 652–662.

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• α-synuclein vaccine engineered for high-titer antibody production & reduction of autoreactive helper T cell response

  Normally, found in healthy brains, accumulation of misfolded alpha-synuclein (α-synuclein) is a hallmark of Parkinson's Disease and also found in Alzheimer's Disease. The presynaptic protein deposits on neurons in the brain in aggregates called Lewy Bodies causing motor degeneration and dementia. Read more>> In this study, an epitope vaccine engineered to contain 3 B-cell epitopes of human α-synuclein strongly induced the production of high-affinity, high-titer anti-α-synuclein antibodies, which are associated with α-synuclein clearance. In addition, to increase vaccine safety, a self helper T cell epitope from tetanus toxin (P30) was engineered to replace a native self epitope in the vaccine, which resulted in the absence of harmful autoreactive helper T cell responses.

  Immunogenicity of epitope vaccines targeting different B cell antigenic determinants of human α-Synuclein: Feasibility study. Ghochikyan A. et al. (2014) Neuroscience Letters 560: 86-91.

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• Optimizing helper T cell response by antigen localization

  Can targeting cellular localization of helper epitope antigens increase their immunogenicity? CD4+ helper T cells are required for the expansion of CD8+ cytotoxic T cells and are helpful in inducing immunity against tumor antigens expressed at low levels or recognized as "self". Incorporating pathogenic antigen sequences (like p30 of tetanus toxin), called helper epitopes, into DNA vaccines have been shown to enhance helper T cell responses against self characterized and low expression antigens. Targeted cellular localization of helper epitopes have been shown to affect their processing and presentation, resulting in changes in overall vaccine immunogenicity. Read more>> In this publication researchers investigate the effects of incorporating localization signals into an HPV DNA vaccine that targeted the helper epitopes p30 and PADRE to the nucleus/cytoplasm, endoplasmic reticulum, or endo/lysosomal compartment. The results showed that increases in immunogenicity were dependent both on helper epitope choice and cellular localization of the epitope. The results suggest that helper epitope localization is an important parameter in DNA vaccine development.

  The effect of helper epitopes and cellular localization of an antigen on the outcome of gene gun DNA immunization. Smahel M et al. (2014) Gene Therapy doi:10.1038/gt.2013.81.

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Immunology

• "Tired" T cells in acute viral infection

  Late nights in the lab can exhaust any scientist, but did you know that T cells get tired too? It's true, memory T cells "tire" during a phenomenon called T cell exhaustion, in which they cease production of immune response stimulatory molecules called cytokines, and express surface receptors that inhibit their own stimulation by antigen contact. Exhaustion lasts anywhere from 24 to 72 hours and occurs just prior to memory T cell division. Understanding the mechanisms of T cell exhaustion is important for developing immunotherapy strategies to fight or protect against cancers and disease. Read more>> Traditionally, T cell exhaustion was believed to be unique to chronic infections and cancers as a result of epigenetic modifications occurring over the duration of the infection. This study, details findings that suggest that T cell exhaustion is a natural part of memory T cell progression after antigen stimulation, by demonstrating that the phenomenon not only occurs in chronic infections, but in acute infections as well.

  CD8+ Memory T Cells Appear Exhausted within Hours of Acute Virus Infection. Hosking MP et al. (2013) J Immunol. 191: 4211-4222.

  • The authors of this publication used GenScript's custom peptide synthesis services and modifications services to perform their study.
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Diabetes

• Bioactive milk-derived peptides target key diabetes/obesity enzyme

  In this study, dipeptides that could be released by enzymatic digestion of milk proteins were found to inhibit dipeptidyl peptidase IV (DPP-IV), an enzyme involved in glucose metabolism. DPP-IV is a key target of incretin-based diabetes and anti-obesity therapies. Inhibition of DPP-IV results in an increase in the levels of incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Increases in GLP-1 and GIP lead to suppression of appetite and increased survival of β cell (cells that secrete insulin), resulting in the lowering of blood glucose levels. The authors of the study suggest that biofunctional hydrolysates could be used to release bioactive dipeptides from milk proteins in the development of novel type 2 diabetes therapeutics.

  Inhibition of dipeptidyl peptidase IV (DPP-IV) by tryptophan containing dipeptides. *Nongonierma AB and FitzGerald RJ (2013) Food and Function. 4: 1843-1849.

  
  

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  • Learn more about the use of milk-derived peptides as therapeutics.

Cancer

• Translational study identifies phosphopeptides as cancer immune system targets

  This study identifies phosphopeptides presented by MHC class-I molecules on tumor cell surfaces as prime targets for therapeutic development. In the study, scientists identified 61 tumor-specific phosphopeptides from a pool of 95 phosphopeptides expressed on primary hematological tumors and normal tissue surfaces. Phosphopeptides were most heavily presented on the surfaces of aggressive and malignant tumor cells. Read more>> Ex vivo assays demonstrated the ability of phophospecific CD8+ T cells to kill leukemia cells and HLA-primary leukemia cells. These findings were strengthened by further clinical studies, which showed that while healthy individuals are capable of generating CD8+ T cell responses against phosphopeptides in the memory compartments of the immune system, leukemia patients show reduced response or none at all. The study emphasized the importance of vaccine development and adoptive T cell immunotherapies against tumor cell surface phosphopeptides.

  MHC Class I-Associated Phosphopeptides Are the Targets of Memory-like Immunity in Leukemia. Cobbold M et al. (2013) Sci Transl Med. 5: DOI:10.1126/scitranslmed.3006061.

  • The authors of this publication used GenScript's custom peptide synthesis services and modifications services to perform their study.
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Epigenetics

• Me3 marks the spot… for mismatch repair

  This study revealed that DNA mismatch repair (MMR) is regulated by methylation of histone 3. Crucial to the discovery was the use of mono-, bi-, and tri-methylated peptides representing methylation states of histone 3 in a GST-pulldown assay. The assay demonstrated that the MMR protein, hMSH6 (specifically the PWWP domain), preferentially binds to lysine 36 of tri-methylated histone 3 (H3K36me3).

  The Histone Mark H3K36me3 Regulates Human DNA Mismatch Repair through Its Interaction with MutSα. Li F et al. (2013) Cell 153: 590-600.

  • The authors of this publication used GenScript's custom peptide synthesis services and modifications services to perform their study.
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Plant Cell Signaling

• New GPCRs? Single pass transmembrane receptors function as GPCRs in plants

  This study challenges conventional GPCR theory. To date, GPCRs have been exclusively considered seven transmembrane (7TM) proteins, however, a study of Gα subunit interactions with the FEA2 receptor in maize suggests that single-pass transmembrane proteins qualify as GPCRs in plants. Read more>> The publication describes the functionality of the membrane-bound Gα protein subunit, which is expressed in maize COMPACT PLANT2. These plants are phenotypically similar to Arabidopsis thaliana CLAVATA pathway mutants. In the study, Gα was revealed to interact in vivo with FEA2, a single-pass, cell surface, leucine-rich repeat (LRR) receptor, and subsequently transmit a signal restricting the growth and proliferation of meristem cells. To date, G proteins have been thought to exclusively interact with 7TM GPCRs. To solidify Gα's role in CLAVATA pathway signaling, maize embryos were grown in media containing synthetic CLV3 peptides, which are normally secreted in vivo, and participate in CLAVATA signaling by binding to LRR receptors. Wild type maize embryos exhibited restricted stem cell growth when exposed to CLV3, but grew normally when exposed to scrambled CLV3 peptides. In contrast, maize embryos lacking Gα grew normally when exposed to scrambled CLV3 peptides, and exhibited reduced restricted stem cell growth when exposed to CLV3, demonstrating the necessity of Gα in meristem growth mitigation. Not only did Gα interact with the single-pass transmembrane FEA2, but, when immunoprecipitated in vivo, Gα did not co-precipitate with any 7TM proteins, suggesting that G proteins in plants are not restricted to signal transmission from conventional 7TM GPCRs.

  Molecular basis for N-terminal acetylation by the heterodimeric NatA complex. Liszczak G et al. (2013) Nat Struct Mol Biol. 20: 1098-1105.

  • The authors of this publication used GenScript's custom peptide synthesis services and modifications services to perform their study.
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siRNA Delivery

• Bee venom peptides deliver siRNA to silence cancer signaling pathways

  This study demonstrates the delivery of siRNAs by peptides derived from a bee venom component called melittin. The peptides (synthesized by GenScript), were used to deliver siRNAs that successfully decreased the production of proteins key to the NFkB pathway, which plays a central role in adult T-cell leukemia/lymphoma (ATLL), suggesting that these peptides could be useful for siRNA-targeted drug delivery. Read more>> The siRNAs were delivered as nanoparticles, which were formed by incubation of melittin-derived peptides (known for membrane destabilization), with siRNA followed by subsequent incubation with albumin (which prevented nanoparticle flocculation). The mechanism of siRNA delivery was determined by a series of assays which revealed that the method of nanoparticle uptake was through macropinocytosis. Nanoparticle disassembly and siRNA release was activated by acidic pH, which was believed to trigger endosomal release of the siRNA cargo into the cytoplasm. When nanoparticles containing siRNAs targeting the p65 and p100/p52 protein subunits of the NFkB pathway were transfected into F8 cells, the amounts of the proteins decreased, indicating the successful silencing of protein expression in the NFkB pathway.

  Mechanisms of Nanoparticle Mediated siRNA Transfection by Melittin-Derived Peptides Hou KK et al. (2013) ACS Nano. 7: 8605-8615.

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• HIV TAT – oligo conjugates developed for photochemically activated gene silencing

  This study addresses two of the major obstacles in siRNA delivery: delivery efficiency and maintenance of oligo cargo activity. The authors address these these challenges by: Read more>> (1) conjugating an antisense DNA oligo to a cell-penetrating peptide, HIV TAT (synthesized by GenScript), via a light cleavable linker and (2) developing a caging technology in which modified caged thymidines were strategically incorporated into the antisense DNA oligos during synthesis. Conjugation of the antisense agents to HIV TAT increased the delivery efficiency without the use of transfection reagents or injection strategies. The conjugation linker and caging technology (both of which are photocleavable) allowed for the external control of antisense agent release, which simultaneously resulted in activation of the antisense agents for gene silencing. The antisense agents delivered using the above strategy were able to silence gene targets in human embryonic kidney and HeLa cells in an efficacious and externally trigger-controlled manner.

  Cellular Delivery and Photochemical Activation of Antisense Agents through a Nucleobase Caging Strategy. Govan JM et al. (2013) ACS Chem Biol. 8: 2272–2282.

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Immunotherapy

• Uncovering the Cancer Immunopeptidome

  100,000 to 750,000 cell surface peptides are expressed for each HLA allele, but only 14,065 peptides are identified in the largest ligandome. Why? The answer stems from the self-tolerance of most tumor-associated peptides, which are derived from wild-type cellular proteins. In cancer patients, these cell surface peptides are recognized by the immune system as "self", allowing cancer cell survival and proliferation. Thus, identification of these potential immunotherapy targets through conventional immunological assays is difficult. Read more>> In a recent PNAS publication, researchers designed an approach to circumvent the obstacle of self-tolerance, which resulted in the identification of 36 epitopes derived from the leukemia-associated antigens, CD20 and myeloperoxidase (MPO). The work was completed using custom peptides from GenScript which were used to create color-coded peptide-HLA multimers.

  Alloreactive cytotoxic T cells provide means to decipher the immunopeptidome and reveal a plethora of tumor-associated self-epitopes. Kumari S, et al. (2013) Proc Natl Acad Sci USA. 20: 652–662.

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