What does oligomerization
mean for drug design and therapeutic efficacy?
Previous authors have emphasized the difficulty of measuring clones of FLCs, as their structures are heterogeneous and can be modified through pH, polymerization, and oligomerization
BGC20-1178 (RS-1178) is a potent inhibitor of neuro-inflammation caused by beta-amyloid while BGC20- 0406 (RS-0406) is a small molecule inhibitor of amyloid oligomerization
(the process by which amyloid self-associates to produce toxic aggregates) and has also been shown to disaggregate already formed amyloid fibrils.
Whatever the case, human synthetic NT-proBNP is a monomer, and the potential confounding issue of analyte oligomerization
is not a problem for this analyte.
The goal of the funded study is to develop pharmaceuticals that can inhibit alpha-synuclein oligomerization
and thus Lewy body formation and neurodegeneration.
Another study demonstrated that the N-terminal region of proBNP contains a leucine zipper-like sequence motif that may induce peptide oligomerization
in plasma under physiologic conditions, producing either a trimer or tetramer of proBNP and a trimer of NT-proBNP (2).
These measurements support the hypothesis of oligomerization
of the glycoprotein.
In vitro characterization of conditions for amyloid-[beta] peptide oligomerization
It is nevertheless important to emphasize that such oligomerization
may have a major influence on antibody detection and assay performance.
Because real-time fluorescence monitoring was not available on the plate reader, we used agarose gel analysis and signal measurements of the Universal Amplifluor-labeled PCR amplicons to assess the contribution of primer oligomerization
in no-template samples to the fluorescent signals.
Moreover, the prosequence contains a leucine zipper-like sequence motif that has been reported to induce oligomerization
of the N-terminal fragments of proBNP and pro-atrial natriuretic peptide (proANP) in plasma (31).
The protein consists of a highly charged acidic amino-terminal domain, which can interact with components of the transcriptional machinery, and a highly charged basic carboxy-terminal region, which can mediate oligomerization
, nuclear localization, and possibly the recognition of damaged DNA.