Vesugen

Vesugen is the synthetic tripeptide Lys-Glu-Asp (abbreviated KED), one of a family of short peptide bioregulators developed at the St. Petersburg Institute of Bioregulation and Gerontology and associated with the work of V. Kh. Khavinson. In the originating literature it is described as derived from a vascular-tissue polypeptide complex and reproduced by chemical synthesis (Khavinson et al., 2021). It is grouped with related ultrashort peptides such as the dipeptide KE (Vilon), the tripeptide EDR (Pinealon), and the tetrapeptide AEDG (Epithalon), and frequently appears as a comparator in structure–activity work. The compound's chemical identity (formula C15H26N4O8; PubChem CID 87571363; ChEBI:159909) is consistent across chemistry databases, and a synthesis route for H-Lys-Glu-Asp-OH is documented in a granted US patent covering peptides investigated in microcirculation research.

The most directly relevant slice of the literature examines KED in vascular endothelial cell cultures. Khavinson and colleagues (2014) studied dissociated vascular endothelial cell cultures from young and aged animals, measuring the proliferation-associated protein Ki-67 and using molecular docking to model peptide interaction with the MKI67 gene promoter; the work characterizes docking contacts within the core promoter region. Kozlov, Khavinson and colleagues (2016) used an in vitro model of normal, atherosclerotic, and restenotic endothelium to examine the relationship between KED and signaling-molecule expression, measuring endothelin-1, connexin-37 (Cx-37), and sirtuin-1 (SIRT1) across culture conditions. These are cell-culture, marker-level measurements characterizing molecular signaling at the cellular level.

A recurring theme across the literature is the hypothesis that ultrashort peptides regulate gene expression through direct DNA binding. A systematic review by Khavinson, Popovich, Linkova and colleagues (2021) compiles evidence from studies examining whether peptides of 2–7 residues can penetrate cell nuclei and interact with histones and with single- and double-stranded DNA. Earlier docking work (Khavinson, Lin'kova, Tarnovskaya, 2016) generated spatial models of DNA–peptide complexes for a set of short peptides and identified candidate binding sites for certain sequences. This body of work frames the proposed mechanism but originates primarily within a small number of collaborating groups; independent replication by unaffiliated laboratories is limited.

KED appears in neurodegeneration-model research, typically alongside the EDR (Pinealon) peptide. In a study using the 5xFAD transgenic mouse model (Khavinson et al., 2021, Pharmaceuticals), investigators measured hippocampal dendritic-spine density and morphology (mushroom, thin, and stubby spine populations) and long-term potentiation, alongside molecular-docking analysis of peptide binding to gene promoters. The docking analysis examined an eight-gene set — including CASP3, NES, GAP43, APOE, SOD2, PPARA, PPARG, and GDX1 — with KED analyzed in parallel to EDR. That article received a 2025 published correction (DOI 10.3390/ph18010111) addressing duplicated figures; the authors stated the scientific conclusions were unaffected. An in vitro amyloid-synaptotoxicity model (Kraskovskaya et al., 2017) used primary hippocampal neuron cultures to measure dendritic-spine counts under KED and EDR treatment.

KED appears in cellular-aging research within the gerontology literature. Sinjari, Diomede, Khavinson and colleagues (2020) studied human periodontal-ligament stem cells and examined whether a set of short peptides including KED was associated with neuronal differentiation markers in that culture system, positioning KED as a tool for studying peptide modulation of cell differentiation. Review articles from the group situate KED among peptides examined for expression of senescence- and proliferation-associated genes during in vitro cell aging.

Because KED is an ultrashort, charged peptide, several modeling studies address candidate cellular uptake mechanisms. Khavinson, Linkova and colleagues (2022; 2023) performed molecular docking of large peptide libraries against the amino-acid transporters LAT1/LAT2 and the peptide transporter PEPT1, examining candidate binding interactions for KED and related peptides. A review by Ilina, Khavinson, Linkova, and Petukhov (2022) situates these transport studies in the context of neuroepigenetic-mechanism research. These are in silico/computational characterizations of candidate transport feasibility, not measured pharmacokinetic data.