Agents have been designed and synthesized which target
the dimerization interface of HIV-1 protease.
These agents, which contain cross-linked peptides from the N- and
C-termini of the protease, both inhibit HIV-1
protease activity and decrease the amount of protease dimer in solution
as measured by size exclusion chromatography,
protein crosslinking, and protease fluorescence studies.
Additionally we have shown that active site-targeted
agents
inhibit HIV-1 protease activity but have little effect on protease
dimerization. These data support the claim that
inhibition with the crosslinked agents is based on a decrease in the
amount of protease homodimer in solution which
in turn is responsible for a decrease in the activity of the
protease.
Self-replication has been demonstrated in synthetic chemical systems based on oligonucleotides, peptides and complementary molecules without natural analogues. However, within a living cell virtually no molecule catalyses its own formation, and the search for chemical systems in which both auto- and cross-catalysis can occur has therefore attracted wide interest. One such system, consisting of two self-replicating peptides that catalyse each other's production, has been reported. Here we describe a four-component peptide system that is capable of auto- and cross-catalysis and allows for the selective amplification of one or more of the products by changing the reaction conditions. The ability of this system selectively to amplify one or more molecules in response to changes in environmental conditions such as pH or salt concentration supports the suggestions that self-replicating peptides may have played a role in the origin of life.
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