Evidence context
Preclinical research
Evidence is preclinical and cell-free/biophysical only, for exact Pinealon (Glu-Asp-Arg / EDR). Directness in this record means direct cell-free biochemical/biophysical interaction only -- it does not establish promoter occupancy in living cells, does not establish named-gene transcriptional regulation, and does not establish in-vivo nuclear target engagement. The primary source (PMID 30762356, Silanteva et al. 2019, Journal of Physical Chemistry B) is the strongest physical-interaction evidence: using spectral/spectroscopic methods, NMR, viscosimetry, molecular-dynamics analysis, and supporting calorimetric work, it reported that EDR partly penetrated/interacted within the DNA major groove and affected DNA-base atoms, particularly guanine N7 and O6, with Mg2+ promoting the interaction by screening negatively charged DNA phosphate groups. No numeric Kd, Ka, stoichiometry, Stern-Volmer constant, or calorimetric affinity value is frozen in this record. The supporting source (PMID 22117547, SRC-PINEALON-002, Fedoreyeva et al. 2011, original Khavinson research lineage) reported two distinct experiments that must remain separated: fluorescence-labeled short peptides including Pinealon were observed in the cytoplasm, nucleus, and nucleolus of HeLa cells, which does not establish identical cellular or nuclear entry for unmodified Pinealon, does not support a blood-brain-barrier-penetration inference, and does not support an in-vivo pharmacologic intracellular-exposure inference; separately, the initial/intact peptide was examined in vitro for interaction with deoxyribooligonucleotides and DNA-ethidium-bromide complexes, showing sequence- and cytosine-methylation-dependent behavior with a biochemical preference within CNG/CAG-containing oligonucleotide sequences. This CNG/CAG preference is biochemical only and must not be read as Pinealon binding all CAG motifs, targeting any named human promoter, or regulating any named human gene from motif presence alone. The 2019 primary source (Silanteva, Komolkin, Morozova, Vorontsov-Velyaminov, Kasyanenko) is independent of the 2011 Khavinson-lineage supporting source, and this record must not be read as the Pinealon-DNA literature being broadly independently replicated. No human anti-aging, longevity-extension, rejuvenation, cognitive-enhancement, Alzheimer's-treatment, neuroprotection, sleep, therapeutic gene-regulation, or safety claim is established by this record.
