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32 Cards in this Set
- Front
- Back
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Involves the cleavage of the amide or peptide bond
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Hydrolysis
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For Human Recombinant IL-11, ____ "hot spots" promote hydrolysis
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Aspartate-proline
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"Hot spots" are peptides containing amino acids such as ____ are degraded more rapidly
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Asn,Asp,Glu, Ser,Ala,Proline, Gln next to Gly, Thr
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Peptides containing amino acids such as Gln or Asn undergo hydrolytic deamidation to produce a
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free COOOH (more acidic)
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Major pathway of protein degradation in both solution and lyophilized formulations
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oxidation
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Oxidation is influenced by:
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temperature and metal ions
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What amino acid is prone to oxidation? It's protection is through?
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cysteine residues, packing under nitrogen
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Racemization occurs through this intermediate?
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carbanion
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What is peptide bonds from racemization susceptible to?
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proteolytic enzymes
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Is denatured proteins more or less soluble than the native protein?
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less soluble
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Four main classes of physical instability in w/c no chemical change occurs but results in an inactive or low activity product
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surface adsorption, precipitation, aggregation, denaturation, fibrilation
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Factors affecting denaturation:
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temperature, pH, organic solvents, and salts (urea, guanidine w/c are carotropic or low hydrogen bonding)
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What term is defined as molecular preference to localize at the interface (solid-liquid or air-liquid)?
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adsorption
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What term is defined where proteins adhere to the wall of the containers or delivery devices and is also refererred to as "frosting"?
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flocculation
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What leads to denaturation?
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adsorption
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What size (small,large) or proteins are more susceptible to adsorption?
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larger proteins
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This may lead to aggregation and precipitation since the hydrophobic inner core of
the protein is exposed at the aqueous phase |
desorption
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This occurs when the hydrophobic regions of a
partially or fully denatured protein interact with each other forming large aggregates |
aggregation
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How is aggregation minimized?
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must maintain protein in its native stable conformation
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Do aggregated proteins retain or lose biological function?
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lose
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This is the macroscopic equivalent of aggregation
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precipitation
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This usually occurs in conjunction with denaturation
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precipitation
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What type of physical instability class/classes does insulin undergo?
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denaturation, precipitation
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What is used to minimize aggregation caused by electrostatic and hydrophobic interactions?
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solubility enhancers
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Does glycosylated or non-glycosylated proteins tend to aggregate and precipitate?
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non-glycosylated
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They include surfactants, phopholipids, and albumin
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anti-adsorption and anti-aggregation agents
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They include phosphate, citrate, and acetate
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buffer components
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They serve to keep the pH of the formulation away from the
isoelectric point (pI) where solubility is usually minimal |
buffer components
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They are formulations rich in methionine, cysteine, tryptophan,tyrosine and histidine are packed under nitrogen or other inert gases
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preservatives and anti-oxidants
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They include ascorbic acid and sodium formaldehyde sulfoxylate
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anti-oxidants
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They are saline and mono- or disaccharide solutions for
parenteral formulations |
osmotic agents
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What is the effect of divalent cations such as Ca++ and Mg++ binding to protein
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reduce solubility – minimized by the addition of chelators such as EDTA (ethylenediamine
tetraacetic acid |
