protein instabilities; protein formualtions Flashcards Preview

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Flashcards in protein instabilities; protein formualtions Deck (19)
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1
Q

what is a protein stabilised by

A
Non-covalent
interactions
• Ionic interactions
• Salt bridges
• Van der Waals
interactions
• Polar interactions
(hydrogen bonds) 

AND

  1. Disulfide bridges
    (between two cysteine
    residues)
2
Q

what can changes in non-covalent interactions result in

A

aggregation
protein
misfolding or unfolding

3
Q

Any changes in the protein environment may trigger

A

r degradation, aggregation

and/or inactivation.

4
Q

name the 5 formulation challenges

A
  • storage stability
  • container and closure systems
  • conformational stability during different steps of manufacturing and formulation process
  • high viscosity of formulations due to requirement for high doses
  • prevent all possible chemical and physical degradation pathways
5
Q

physical protein instabilities

A

aggregation

6
Q

chemical protein instabiltities

A

cross link
oxidation
hydrolysis
mail lard reaction

7
Q

factors affecting protein stability

A
Temperature
• pH
• Ionic strength (salts and non-aqueous solvents)
• Metal ions and chelating agents
• Protein concentration
• Surface
8
Q

how does temp affect proteins

A

As you increase temp, you change the energetics of system, protein unfolds, more energy in, protein melts and unfolds

9
Q

how does ph affect proteins

A

At isoelectric point; pH is 0 and they will be affected.

10
Q

which proteins are more prone to degdration

A

• Denatured/unfolded proteins

11
Q

which reaction is the the most common degradation reaction

A

deamidation

12
Q

which proteins are most prone to deamidation

A

glut and asparagine

13
Q

what does deamidation depend on

A

ph

14
Q

whihc side chains are prone to oxidation

A

his met cys trp and tyr

15
Q

where do oxidation reactions take place

A

presence of
transition metal ions or
upon exposure to light

16
Q

which bonds are prone to hydrolysis

A

Bonds between

Asp-Gly and AspPro

17
Q

which amino acids are prone to racemic conversion

A

all amino acids apart from gly

18
Q

what is rate of isomerisation influenced by

A

location and the
mobility of the amino
acid side chain

19
Q

Aspartic acid and
asparagine can form
isoaspartic acid via which intermediate

A

succinimide

intermediate

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