PS400 exam 3 Flashcards
(44 cards)
for ph profile, when is the max stability of a drug?
at pka, drug segregation rate is lowest
formulate ate aka or a little above
what is best selling drugs for the years:
2012-2020
2021-23
23-24
24
humira (anti TNF a antibody)
cominrnaty (covide 19 mrna)
keytrude (anti PD1)
ozemspic & Wegovy
what are features of small molecule drugs?
low MW
organic or chemical synthhesis
fewer steps
well characterized
known structure
homogenous
not immunogenic
what are properties of biologics?
high MW
made w/ live cells or organisms
critical steps
less easily characterized
may or may not be defined
heterogenous
immunogenic
what can cause precipitation in plasma products?
ethanol, salt, pH, temp, centrifuge
what are peptide products?
calcitonin
oxytocin
vasopressin
what is the general mechanism of peptide production?
deprotection of chains
coupling of growing chain with new aa
cleavage of peptide chain
on a large scale, produced by recombinant DNA technology
why are protein therapeutics more complicated than small molecule therapeutics??
large and more complex
how are protein therapeutics produced?
recombinant by living organisms
challenging to characterize, require many analytical methods
what is affect of protein therapeutics for immunogenicity and why?
potential for immunogenicity, due to endotoxins
what happened during hGh testing??
developing fevers due to endotoxins
they must be removed by methods including ion-exchange chromatography
what is primary, secondary, and tertiary and quaternary structure?
primary: sequence of a chain
secondary: local folding of polypeptide into helices or sheets
tertiary: 3d folding pattern of protein
quaternary: protein consisting more than one amino acid
what is the process of endotoxin removal?
ion exchange chromatography
mix aa–>
binding of negative aa with cations to immobilize–>
separation of negative charged aa
how are protein therapies produced??
isolate gene of interest
introduce gene into an expression vector
transform/ transfect vector into host cells
grow cells
isolation and purify protein from cells
formulate protein product
what is the general structure of antibodies?
4 polypeptide chains connected by disulfide bonds between cysteine residues
2 heavy: Fab
2 light: fc
how do Herceptin antibodies work?
immune cells targeting cancerous cells bound by Herceptin
dimersed HER2 receptors signal tumor cells to proliferate
what does Herceptin do?
binds to HER2 tumor cells and flag them for destruction by immune system
blods downstream HER2 signaling to inhibit proliferation
how does neonatal Fc receptor recycling work?
FcRn binds IgG in acidified endosome
sorting of complexes
some are recycled and IgG disassociate at physiological pH
OR
non receptor proteins are degraded in lysosome
how does ADCC and CDC work?
ADCC:
-antibodies bind antigens
-NK cells recognize cell bound antibodies
-cross linking degranulation into lytic synapse
-die via apoptosis
CDC:
same process except for step 2
recruits complementary proteins that form membrane attack complex
what are the 5 classes of antibodies?
IgM
igA
igD
igG
igE
what is the most common subclass of IgG?
IgG1 and IgG2 & 4 r common
what is fucosylations?
what does it do?
adding focose sugar units to a molecule
on Fc domain of antibody adds bulk–> weakens binding to Fc-y receptors for ADCC
what is deamination degradation pathways?
what is rate affected by?
Asn & Gln
faster for Asn than Gln
N+1 residue (asn-gly is fastest)
reduces potency and leads to aggregation
what is the process for oxidation?
what is it caused by?
what happens to trp?
when does it occur faster?
met, trp, cys
caused by chemical reagents (excitants,surfactant ) UV light
oxidation of trp by light can become yellow
reduces potency and less to aggregation
occurs faster at higher temp
