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

Glaucio Monteiro Ferreira; Thales Kronenberger; Éryka Costa de Almeida; Joseane Sampaio; Clélia Ferreira Terra; Ernani Pinto; Gustavo Henrique Goulart Trossini

doi:10.3390/molecules24234369

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

Molecules. 2019 Nov 29;24(23):4369. doi: 10.3390/molecules24234369.

Authors

Glaucio Monteiro Ferreira¹, Thales Kronenberger², Éryka Costa de Almeida³, Joseane Sampaio³, Clélia Ferreira Terra⁴, Ernani Pinto³, Gustavo Henrique Goulart Trossini¹

Affiliations

¹ Department of Pharmacy, School of Pharmaceutical Sciences, University of São Paulo, Av Prof Lineu Prestes, 580, Bl. 13, São Paulo/SP CEP 05508-000, Brazil.
² Department of Oncology and Pneumology, Internal Medicine VIII, University Hospital Tübingen, Otfried-Müller-Straße 10, DE 72076 Tübingen, Germany.
³ Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, Av Prof Lineu Prestes, 580, Bl. 17, São Paulo/SP CEP 05508-000, Brazil.
⁴ Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av Prof Lineu Prestes, 748, Bl. 12, São Paulo/SP CEP 05508-000, Brazil.

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.

Keywords: Microcystis; aminopeptidase inhibition; cyanobacteria; microginin; molecular modelling.

MeSH terms

Animals
Bacterial Proteins / chemistry*
CD13 Antigens* / antagonists & inhibitors
CD13 Antigens* / chemistry
Microcystis / chemistry*
Models, Molecular*
Oligopeptides / chemistry*
Protease Inhibitors / chemistry*
Swine

Substances

Bacterial Proteins
Oligopeptides
Protease Inhibitors
CD13 Antigens