Bioactive peptide inhibiting aminopeptidase M (aminopeptidase N) Probestin

Probestin, having a proline-proline sequence in its structure, was isolated from fermentation broth of Streptomyces. Probestin strongly inhibited aminopeptidase M (AP-M, and AP-N) in M1 family of aminopeptidases.¹⁾
AP-M is known as an enkephalin degrading enzyme²⁾, and various other functions have also been reported. ³⁾ So the bioactive peptide is considered to be a useful tool for biochemical, cell biological, and pharmacological studies. In addition, it was reported that radiolabeled probestin derivatives were used as molecular imaging reagents for AP-M (AP-N) by utilizing high affinity of probestin towards AP-M (Ki: 1.9×10^-8 M).^1,4)
* This product is for research use only.

Structure of Probestin (#00367)

Aminopeptidase M (EC 3.4.11.2) which is also know as AP-M, membrane alanyl aminopeptidase, and microsome aminopeptidase, was initially isolated from microsome membrane fractions prepared from porcine kidney by Pfleiderer and Celliers.⁵⁾ In 1980, it was proposed that the name of the enzyme should be changed to aminopeptidase N (AP-N) because its enzymatic preference is to neutral amino acid residues.⁶⁾ Then, the new name of the enzyme is widely used these days.
It has also been clarified that AP-M (AP-N) is actually the same protein of CD13 which expresses the cell surface of bone marrow progenitor cells, monocytes, and granulocytes.⁷⁾
Molecular weight of AP-M (AP-N, CD13) is 110 KDa and the enzyme is a metalloprotease 2 which belongs to peptidase family M1. AP-M has different isozymes and is a universal enzyme existing in a variety of organs, tissues, and cell types such as endothelial cells, epithelial cells, fibroblasts, and leukocytes. It is also known that the enzyme relates tumor formulation, immune system, and pain sensation, and functions as a virus receptor to corona virus and other human viruses. In addition to the expression of the variety of functions, AP-M relates antigen trimming and antigen presentation.
The multiple functions of AP-M facilitate regulation of functional peptide-mediated response such as pain sensation and vasopressin secretion and affect several important biological process such as immune function, cell growth, secretion, infiltration, angiogenesis, and so on. Therefore, the development of new therapies targeting AP-M is of interest.³⁾

■ Inhibitory activity of probestin against various aminopeptidases (Cited from Ref. 1)

*Biological activity of the product was not verified. The values shown above were cited from the references.