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