Inhibition of Porcine Aminopeptidase M (pAMP) by the Pentapeptide Microginins.

Abstract

Aminopeptidase M (AMP) inhibition is of interest for several diseases, such as highly vascularized cancer types. AMP can be inhibited by linear pentapeptides isolated from Microcystis aeruginosa LTPNA08 (MG7XX). Porcine AMP inhibition-a model for human AMP-activity was spectrophotometrically measured by the formation of p-nitroanilide from L-leucine-p-nitroanilide substrate by AMP. AMP inhibition by MG770 exhibited comparable inhibition levels to amastatin (IC50 values: 1.20 ± 0.1 μM and 0.98 ± 0.1 μM, respectively), while MG756 was slightly less potent (with IC50 values of 3.26 ± 0.5 μM). Molecular modelling suggests a potential binding mode, based on the interaction with the Zn2+ cofactor, where MG770's extra methyl group contributes to the disturbance of the Zn2+ cofactor complex and highlights the importance of hydrophobicity for the site.

• Authors: Glaucio Monteiro Ferreira, Thales Kronenberger, Éryka Costa de Almeida, Joseane Sampaio, Clélia Ferreira Terra, Ernani Pinto, Gustavo Henrique Goulart Trossini
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 24 Issue 23 (Nov 29 2019) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 31795383 (Publication Type: Journal Article)

Chemical References

• Bacterial Proteins
• Oligopeptides
• Protease Inhibitors
• CD13 Antigens

Topics

• Animals
• Bacterial Proteins (chemistry)
• CD13 Antigens (antagonists & inhibitors, chemistry)
• Microcystis (chemistry)
• Models, Molecular
• Oligopeptides (chemistry)
• Protease Inhibitors (chemistry)
• Swine