Stability biologics

Question 1

Protein structure

Answer 1

-linear chain aminos
-peptide bond
-folds
-disulfide, H bonds, ionic interactions
-maybe glycosylated

Question 2

Biologic issues

Answer 2

-more fragile
-large = more bonds to break
-could unfold=lose activity
-aggregate

Question 3

biologics

Answer 3

-protein
-recombinant proteins, vax, stem cells, gene therapy

Question 4

Protein drug degradation

Answer 4

-chemical (break form bonds): hydrolysis, oxidation

-physical (change structure): unfolding, aggregation

Question 5

Hydrolytic reactions

Answer 5

-Asparagine (Asn) deamidation
-peptide bond hydrolysis

Question 6

oxidation reactions

Answer 6

-methionine (met) oxidation
-disulfide bond scrambling

Question 7

Asparagine (Asn) structure

Answer 7

-deamidation cause loss of amine group as ammonia

Question 8

methionine oxidation

Answer 8

S to S=O to O=S=O

Question 9

Disulfide scrambling

Answer 9

-aggregation
-reactive species (RS-)
RSSR +R’SH <–> R’SSR +RSH

Question 10

Aggregation

Answer 10

=cloudy
-activity increase or decrease
-bad response
-low levels hard to detect

Question 11

prevent degradation of protein drugs

Answer 11

-no heat
-no light
-no moisture
-no oxygen
-no metals
-no shaking (aggregation)

Question 12

Proteins can degrade by

Answer 12

-methionine Ox
-Disulfide scrambling OX
-Asparagine deamindation Hydro
-peptide bond hydrolysis
-aggregation