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.
Second
harmonic generation (SHG) microscopy measurements indicate
that inkjet-printed racemic solutions of amino acids can produce nanocrystals
trapped in metastable polymorph forms upon rapid solvent evaporation.
Polymorphism impacts the composition, distribution, and physico-kinetic
properties of organic solids, with energetic arguments favoring the
most stable polymorph. In this study, unfavored noncentrosymmetric
crystal forms were observed by SHG microscopy. Polarization-dependent
SHG measurement and synchrotron X-ray microdiffraction analysis of
individual printed drops are consistent with formation of homochiral
crystal production. Fundamentally, these results provide evidence
supporting the ubiquity of Ostwald’s Rule of Stages, describing
the hypothesized transitioning of crystals between metastable polymorphic
forms in the early stages of crystal formation. Practically, the presence
of homochiral metastable forms has implications on chiral resolution
and on solid form preparations relying on rapid solvent evaporation.
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