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An FT-IR Study on Packing Defects in Mixed β-Aggregates of Poly(l-glutamic acid) and Poly(d-glutamic acid): A High-Pressure Rescue from a Kinetic Trap
Under favorable conditions of pH and temperature, poly(l-glutamic acid) (PLGA) adopts different types of secondary
and quaternary structures, which include spiral assemblies of amyloid-like
fibrils. Heating of acidified solutions of PLGA (or PDGA) triggers
formation of β<sub>2</sub>-type aggregates with morphological
and tinctorial properties typical for amyloid fibrils. In contrast
to regular antiparallel β-sheet (β<sub>1</sub>), the amide
I′ vibrational band of β<sub>2</sub>-fibrils is unusually
red-shifted below 1600 cm<sup>–1</sup>, which has been attributed
to bifurcated hydrogen bonds coupling CO and N–D groups
of the main chains to glutamic acid side chains. However, unlike for
pure PLGA, the amide I′ band of aggregates precipitating from
racemic mixtures of PLGA and PDGA (β<sub>1</sub>) is dominated
by components at 1613 and 1685 cm<sup>–1</sup>typically
associated with intermolecular antiparallel β-sheets. The coaggregation
of PLGA and PDGA chains is slower and biphasic and leads to less-structured
assemblies of fibrils, which is reflected in scanning electron microscopy
images, sedimentation properties, and fluorescence intensity after
staining with thioflavin T. The β<sub>1</sub>-type aggregates
are metastable, and they slowly convert to fibrils with the infrared
characteristics of β<sub>2</sub>-type fibrils. The process is
dramatically accelerated under high pressure. This implies the presence
of void volumes within structural defects in racemic aggregates, preventing
the precise alignment of main and side chains necessary to zip up
ladders of bifurcated hydrogen bonds. As thermodynamic costs associated
with maintaining void volumes within the racemic aggregate increase
under high pressure, a hyperbaric treatment of misaligned chains leads
to rectifying the packing defects and formation of the more compact
form of fibrils