# Molecular and Structural Characterization of an Immunopurified Telomerase from Leishmania major and the Effect of Telomerase Inhibitors

## TL;DR

Researchers studied telomerase in Leishmania major, a parasite causing leishmaniasis, and found that human telomerase inhibitors can also block its activity, suggesting new treatment possibilities.

## Contribution

The study characterizes L. major telomerase and shows that human telomerase inhibitors can inhibit its activity and cell growth.

## Key findings

- Telomerase activity in L. major elutes as a 600 KDa complex.
- MST-312 and TMPYP4 inhibit L. major telomerase and cell growth.
- Telomerase is critical for the replicative forms of L. major.

## Abstract

Leishmania major is the etiological agent of cutaneous leishmaniasis (CL) in several countries in Asia and Northern Africa. The disease is considered a zoonotic infection where rodents are the reservoirs and phlebotomine sandflies are the vectors. Once inside the human body, the parasite multiplies inside the macrophages of infected patients, but the disease eventually cures spontaneously, leaving scars where the phlebotomine bites occurred. Given the importance of the replicative forms in the parasite’s cell cycle, here, we decided to study the enzyme telomerase, which has the critical role of replenishing the chromosomal telomeric ends during cell replication. To this aim, we first conducted partial purification using Sephacryl-300 HR gel filtration, which allowed us to determine that the telomerase activity eluted as a 600 KDa complex. Second, we characterized an immunopurified L. major telomerase, and to try to explain some of our findings, we performed modeling studies using Alfa fold 3, Pyre2, and Swiss Protein Model. Finally, considering the similarity between the catalytic site of Leishmania and Homo sapiens telomerase, we decided to test typical inhibitors of human telomerase on the purified enzyme and promastigote cell forms, confirming that MST-312 and TMPYP4 efficiently inhibited L. major activity and arrested cell growth in Leishmania promastigotes. Our findings confirm the importance of telomerase activity in L. major’s replicative forms and suggest the possibility of using drugs previously tested on human telomerase to treat CL.