Carboxypeptidase A Substrate: Ac-Thia-Phe

Pancreatic cancer is the fourth and fifth leading cause of carcinoma death in the US among men and women, respectively, partially due to the lack of sensitive, diagnostic markers for early detection. Carboxypeptidase A (CPA) is an important enzyme of the pancreas and marker of pancreatic disease. Most recent findings suggest it may also act as a marker of pancreatic cancer.1,2 Its activity can be detected using the dipeptide mimetic substrate, acetyl- L-phenylalanyl-L-thiaphenylalanine, or Ac-Phe-Thiaphe-OH. Matsugi, et al., presented data that indicated both active form and total CPA serum levels may be useful for early detection of pancreatic carcinoma, using Ac-Phe-Thiaphe- OH substrate to detect CPA activity. These new findings may offer hope for improved survival rates for a disease that is nearly always fatal.

Carboxypeptidase A is a digestive enzyme that hydrolyzes the carboxyl-terminal peptide bond but works best when the C-terminal residue possesses an aromatic or a bulky aliphatic side chain. CPA can be conveniently assayed using the dipeptide mimetic substrate, acetyl-l-phenylalanyl-l- thiaphenylalanine. Hydrolysis of this substrate provides the unusual amino acid thiaphenylalanine which rapidly degrades to thiophenol. Utilizing Ellman’s reagent to as- say free thiol content provides a quantitative analysis of enzyme activity. Leucine aminopeptidase has also been quantified using the dipeptide by Gilvarg and coworkers. The substrate is currently available in research quantities; please inquire for bulk amounts.



  1. P. Shamamian, et al., Gastroenterology, 113, 232 (1998).
  2. P. Shamamian, et al., Hepato Pancreato Biliary J., 8, 451 (2006).

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