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

Author(s)

Ferreira, Glaucio Monteiro ^[1] ; Kronenberger, Thales ^[2] ; de Almeida, Eryka Costa ^[3] ; Sampaio, Joseane ^[3] ; Terra, Clelia Ferreira ^[4] ; Pinto, Ernani ^[3] ; Goulart Trossini, Gustavo Henrique ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Pharm, Av Prof Lineu Prestes 580, Bl 13, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Hosp Tubingen, Dept Oncol & Pneumol, Internal Med 8, Otfried Muller Str 10, DE-72076 Tubingen - Germany

^[3] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Av Prof Lineu Prestes 580, Bl 17, BR-05508000 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Inst Chem, Dept Biochem, Av Prof Lineu Prestes 748, Bl 12, BR-05508000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Molecules; v. 24, n. 23 DEC 2019.
• Web of Science Citations: 0

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 mu M and 0.98 +/- 0.1 mu M, respectively), while MG756 was slightly less potent (with IC50 values of 3.26 +/- 0.5 mu M). 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. (AU)

• FAPESP's process: 14/50420-9 - Secondary metabolites from aquatic microrganisms and their impact on seafood and freshwater fish aquaculture
• Grantee: Ernani Pinto Junior
• Support Opportunities: Regular Research Grants