Term
| advantages to recombinant proteins |
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Definition
| limited natural product sources, cheaper than natural products, AVOIDs immunogenicity, avoids pathogen contamination |
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Term
| advantages over small molecules |
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Definition
| MOA of therapeutic targets are complex and impossible to target with low molecular weight |
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Term
| disadvantages of recombinant DNA |
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Definition
| not evolved to be good drugs, complex production, tend to aggravate and susceptible to proteases in vivo |
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Term
| plasmids for recombination (protein synthesis in E coli) |
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Definition
| must have origin of replication and selection markers and maintained in an episome, also offers easy manipulation and modification |
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Term
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Definition
| cytoplasmic aggregates of proteins that occur during synthesis within E cli |
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Term
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Definition
| post-transLATIONAL modifications that does not occur naturally in E coli |
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Term
| E coli protein synthesis limitations |
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Definition
| proteins that do not require glycosylation (post-translations modification), other PTM do not occur the same as eukaryotic cells (disulfide bonds and proteolysis) |
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Term
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Definition
| Post-translational modification in which N-terminus is cleaved off the end of proteins within the endoplasmic reticulum |
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Term
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Definition
| post-translational modification of secreted proteins that occur within compartments of eukaryotic cells |
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Term
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Definition
| stimulates growth/differentiation of T cells and NK cells, stimulates AB production in B cells |
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Term
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Definition
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Term
| IFN-beta (Interferon beta) |
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Definition
| affects many cells types, induces antiviral genes, enhances MHC-class I expression |
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Term
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Definition
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Term
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Definition
| stimulate erythropoeisis (increases RBCs), treats anemia |
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Term
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Definition
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Term
| G-CSF (granulocyte colony stimulating factor) |
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Definition
| cytokine promoting hematopoiesis |
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Term
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Definition
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Term
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Definition
| retains full biological activity, however they are less soluble because glycans improve solubility |
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Term
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Definition
| made within E coli and CHO cells, glycans improve stability in CHO products |
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Term
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Definition
| requires glycosylation for stability and to reduce aggregation, exclusively made in mammalian cells |
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Term
| insulin; overcoming PTM E coli production |
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Definition
| Bchain:C-peptide:Achain, C-peptide cleaved in ER allowing for A and B chain to associate via two disulfide bridges, A and B chains initially produced separately |
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Term
| proteins produced in E coli that form inclusion bodies |
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Definition
| must be solubilized and refolded, modifying cystine residues to produce proper folding is often employed |
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Term
| Proleukin (IL-2); protein stability |
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Definition
| mutate cystine into serine (Cys125ser) to improve stability |
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Term
| cystines within native IL-2 |
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Definition
| 58, 105, 125, two form disulfide bond and the other remains reduced, presence of reduced cystine encourages aggregation |
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Term
| Betaferon and Betaseron (IFN-beta-Ib) |
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Definition
| first cystine is removed (cys17ser) |
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Term
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Definition
| eukaryote that perform some PTMs like glycosylation, short generation time, easily cultured |
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Term
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Definition
| deletion of genes that "hyper-mannosylate" proteins and induction of genes that produce human glycosylation structures |
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Term
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Definition
| Chinese hamster ovary commonly used for mammalian cell line protein production |
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Term
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Definition
| introduced anti-apoptosis genes, introduced chaperones (proteins that facilitate folding) |
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Term
| kerinocyte growth factor (KGF); prevents chemotherapy/ radiation-induced mucositis |
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Definition
| aggregation occurs during storage of proteins after synthesis, REMOVAL of 23-N-Terminal amino acid improve stability |
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Term
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Definition
| KGF with removed 23-N-terminal amino acid with improved stability and decreased aggregation |
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Term
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Definition
| point mutation in B chain to improve therapy (pro28lys, and lys29pro) allowing drug to stay in monomer form resulting in rapid action |
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Term
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Definition
| point mutation to improve therapy (pro28asp) allowing drug to stay in monomer form resulting in rapid action |
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Term
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Definition
| EPO; darbepoetin alpha containing two additional N-linked carbohydrates which increases half life |
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Term
| darbepoetin pros and cons |
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Definition
| 3-fold increase in serum in half life however there a 5 fold reduction in receptor binding affinity relative to epoeitin-alpha |
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Term
| difference in rodent glycosylation compared to human |
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Definition
| missing 2,6-linked sialylation and has other different components that ilicit immunogenic reactions |
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Term
| Erbitux (epidermal growth factor receptor) |
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Definition
| induced hypersensitivity reactions, ABs against galactose alpha 1,3 galactose which is present on Fab portion of heavy chain |
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Term
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Definition
| synthetic isoform of interferon; 'consensus IFN' and corresponding DNA sequenced was synthesized |
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Term
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Definition
| potent antiviral activity, NK cell activation and cytokine induction |
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Term
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Definition
| genetic fusions to Ig Fc or albumin |
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Term
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Definition
| fusion of two proteins or domains of two proteins allows modification of activity |
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Term
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Definition
| fusion that is common and improves stability of proteins |
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Term
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Definition
| have long half-life with extraordinary serum concentrations compared with other circulating proteins |
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Term
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Definition
| chimera, pH-dependent, binding allows recycling of Fc or albumin-bound fusion proteins |
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Term
| albumin-interferon chimera |
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Definition
| IFN, insulin, IL-2 fusion have been attempted and increased half-life but there is some risk of immunogenicity |
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Term
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Definition
| cytokine with many functions, pyrogen, inflammation and apoptosis inducer, potent chemoattractant for neutrophils |
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Term
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Definition
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Term
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Definition
| captures TNF before it attaches to immune cells, attaching Fc causes dimerization and results in longer serum half-life |
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Term
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Definition
| affects hydrophobicity (improved solubility) and electrostatic interactions, increases protein size, reduced immunogenicity (can) and proteolysis |
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Term
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Definition
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Term
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Definition
| PEGylated human growth hormone (HGH receptor antagonist) |
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Term
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Definition
| PEGylated interferon alph (ITN-alpha) |
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