Forte and Michael Oda have developed functional apolipoprotein
A-1 (apoA-1) mutant proteins and their encoding polynucleotides
that increase the anti-oxidating activity of paraoxonase (PON)
by as much as 30% compared to the effect of naturally occurring
apoA-1. A single post-operative dose of a drug based on the
Berkeley Lab apoA-1 variants could reduce the probability
of restenosis and alleviate the harmful oxidative effects
of acute phase response, thereby reducing the frequency of
repeated invasive procedures.
The Berkeley Lab researchers modified the natural form of
the DNA encoding human apoA-1 to introduce a series of restriction
sites. These restriction sites facilitated the creation of
three unique mutation forms of apoA-I which contain a cysteine
substitution at amino acid positions 10, 27 and 61, respectively.
These cysteine substitutions are correlated with a significant
increase in PONs anti-oxidating activity. Indications
are that the cysteine on apoA-1 serves to enhance the efficiency
of PONs enzymatic activity but does not increase the
amount of the enzyme. HDL bearing multiple apoA-1 mutant proteins
may possess further elevated PON activity.
REFERENCE NUMBER: IB-1713