Cartalax

Cartalax is the name used in the St Petersburg short-peptide literature for the synthetic tripeptide Ala-Glu-Asp, abbreviated AED (Khavinson et al., 2021). Earlier papers from the same group code it T-31 (Khavinson et al., 2014). It belongs to the short peptides that V. Kh.

Khavinson's group at the St Petersburg Institute of Bioregulation and Gerontology calls peptide bioregulators; the group's table links it to cartilage and skin fibroblasts. The Cartalax peptide has a small literature, about 20 PubMed records, nearly all from that institute and its collaborators.

PubChem CID 87815447 lists the same formula, weight and CAS number, and the formula and weight follow from the sequence, so the sources agree. One MeSH entry term, also among PubChem's synonyms, reads H-Asp-Glu-Asp-OH, a different sequence from the Ala-Glu-Asp both records describe.

Published work on AED falls into five areas, each summarized below with its model. Searching PubMed for the name, the T-31 code, the sequence and the abbreviation finds 16 primary or modeling papers plus reviews. All but one include Khavinson or a colleague from his institute; the exception, a Ukrainian kidney group, wrote its other AED papers with that institute. Seven are in Russian, nearly all test AED beside other peptides or an extract, and all of it is cell, explant, docking or rat work.

Cartilage and chondrogenic cell models

Despite the name, direct cartilage work is recent and thin. In chondrocyte cultures, AED and a cartilage polypeptide complex were both reported to bring the aging-associated rise in p16, p21, p53, TNF-α and IL-1α, and the fall in sirtuin-1, back toward normal (Myakisheva et al., 2023).

In human mesenchymal stem cells during replicative aging, AED at 200 ng/mL raised expression and synthesis of the chondrogenic markers SOX9, aggrecan, type II collagen and COMP, while the complex needed 2,000 ng/mL (Myakisheva et al., 2023). Both are in Russian; we read their English abstracts. The group's 2022 review calls AED a chondroprotector, citing a 2008 Russian patent rather than a published study (Khavinson et al., 2022).

Bone in rats

In ovariectomized rats, a substance coded T-31 (identified as AED in the group's later papers) and a cartilage extract preparation both prevented the fall in bone mineral density and raised density already lost, the extract significantly more (Povorozniuk et al., 2007).

In old rats with a standard defect in the lower jaw, Cartalax started 30 days before surgery left early repair similar to controls, but at 60 to 120 days the new tissue held less connective tissue and cartilage and showed more advanced bone remodeling than in controls or in rats started at surgery (Slugina et al., 2016).

Skin fibroblasts

In skin fibroblasts aging in culture, AED was one of four peptides that lowered MMP-9 and raised Ki-67 and CD98hc, and one of two, with epitalon (AEDG), that also suppressed caspase-dependent apoptosis (Lin'kova et al., 2016). In human skin fibroblasts during replicative aging, it raised synthesis of sirtuin-1, sirtuin-6 and collagen I (Fridman et al., 2020).

Kidney cells and rat kidney models

Much of the AED literature concerns the kidney, a tissue the group's 2022 table assigns to another tripeptide, EDL (Khavinson et al., 2022). In aging primary kidney cell cultures, T-31 (AED) and a calf kidney polypeptide complex were reported to activate cell renewal, judged by Ki-67 and p53 (Khavinson et al., 2014), and a Russian-language follow-up reported more proliferation, lower p16, p21 and p53, and higher SIRT-6 with AED or EDL (Khavinson et al., 2014).

In kidney explants from young and old rats, AED and EDL stimulated proliferation and reduced apoptosis, less than the complex did (Chalisova et al., 2015). In rats with cisplatin-induced acute renal failure, AED lowered urinary protein excretion and urine electrolytes, while EDL, epitalon and the complex normalized more measures (Zamorskii et al., 2015).

Stem cells, gene expression and a thymocyte test

In the human embryonic bone marrow mesenchymal stem cell line FetMSC, aged by passaging or stationary culture, AED, KED (vesugen) and KE at nanomolar concentrations raised expression of IGF1, by 3.5 to 5.6 fold, and of NFκB (Ashapkin et al., 2020). In human periodontal ligament stem cells cultured with 0.01 µg/mL of AED, three related peptides or all four, each raised GAP43 staining, but western blots credited the GAP43 and nestin rises to the mixture and KED (Caputi et al., 2019).

In aging thymocyte cultures, T-31 was tested with two other peptides, and only AB-9 showed a combined effect on proliferation, differentiation and apoptosis (Lin'kova et al., 2011). For AED, the group's proposed mechanism of direct DNA binding (Khavinson et al., 2021) rests on docking, which placed it in the minor groove of an alternating AT sequence (Khavinson et al., 2014).