Lead-like compounds for inhibiting Methionine amino peptidase 2 (MetAP2)

This research aims to find a new approach to deal with cancer, by targeting a protein that controls the growth and increases the size of the tumour. The approach uses computer-aid drug designed to find the best drug for inhibiting f Methionine Aminopeptidase (Metap2) which is an enzyme that is responsible for starting the synthesis of new protein. The inhibition of the enzyme was found to be crucial in stopping the growth of the tumour and its development. In this research, an in-silico approach was conducted to obtain compounds that are capable of inhibiting the enzyme with non-toxic features. This is done by using Ligand-Based. The Zinc15 and National Institute of Cancer Data (NCI) Databases were screened to attain a variety of manufactured Compounds. Then, molecular docking filtration process was carried out using PyRx, and Autodock4. Finally, SwissADME protocol was used to show the ADMET properties and that compounds can permit the blood barriers and validate better pharmacokinetic properties than the Fumagillin.

Structure-Function and Industrial Relevance of Bacterial Aminopeptidase P

Aminopeptidase P (APPro, E.C 3.4.11.9) cleaves N-terminal amino acids from peptides and proteins where the penultimate residue is proline. This metal-ion-dependent enzyme shares a similar fold, catalytic mechanism, and substrate specificity with methionine aminopeptidase and prolidase. It adopts a canonical pita bread fold that serves as a structural basis for the metal-dependent catalysis and assembles as a tetramer in crystals. Similar to other metalloaminopeptidase, APPro requires metal ions for its maximal enzymatic activity, with manganese being the most preferred cation. Microbial aminopeptidase possesses unique characteristics compared with aminopeptidase from other sources, making it a great industrial enzyme for various applications. This review provides a summary of recent progress in the study of the structure and function of aminopeptidase P and describes its various applications in different industries as well as its significance in the environment.

Methionine Aminopeptidase 2 as a Potential Target in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is an aggressive metastatic cancer with a very low survival rate. This tumor is hypovascularized and characterized by hypoxic regions, yet they are not impeded by the oxidative stress in their microenvironment. PDA’s high resilience raises the need to find new effective therapeutic targets. This study investigated methionine aminopeptidase 2 (MetAp2) — a metallopeptidase known to play an important role in tumor progression — as a potential target for treating PDA by blocking its activity. Immunohistology of patient-derived PDA tissue sections revealed high expression of MetAp2 in metastatic regions compared with primary sites. Pancreatic cancer cells (cell lines and patient derived) exhibited high expression levels of MetAp2 and significant inhibition of proliferation upon exposure to a selective MetAp2 inhibitor. The growth of Orthoptic pancreatic PancOH7 tumors in mice was significantly suppressed when MetAp2 inhibitor was administered orally. Our finding revealed that the inhibition of MetAp2 in cells was associated with a significant reduction in glutathione (GSH) levels, a substance known for its role in alleviating oxidative stress, which suggests a possible rationale for the anti-cancer activity in highly hypoxic tumors such as PDA. Taken together, our results indicate that MetAp2 can be a studied as a target in PDA and possibly in other tumors with high expression levels of MetAp2 which are not necessarily highly angiogenic tumors.