Serine protease prostate specific antigen

In 2002, the condensation of the titanium enolate derived from 2-pyridylthio acetoxyacetate with /V-4-methoxvphenvlimine of (S)-0,0-cyclohexylidene protected glyceraldehyde has been reported to give (35.4/C4 A)-p-lactam as a single product in 65% isolated yield (Scheme 52), [137]. A reactions sequence at C-3 and C-4 led in good yield to the p-lactam inhibitor of the serine protease prostate-specific antigen. 

Scheme 52 Stereoselective synthesis of (3-lactam inhibitor of the serine protease prostate-specific antigen...

Veinberg G, Vorona M, Shestakova I, Kanepe I, Lukevics E (2003) Some of the more notable advances concern the development of mechanism-based serine protease inhibitors of elastase, cytomegalovirus protease, thrombin, prostate specific antigen, and cell metastasis and as inhibitors of acyl-CoA cholesterol acyl transferase. Curr Med Chem 10 1741... 

Takayama TK, McMullen BA, Nelson PS, Matsumura M, Fujikawa K. Characterization of hK4 (Prostase), a prostate-specific serine protease Activation of the precursor of prostate specific antigen (pro-PSA) and single-chain urokinase-type plasminogen activator and degradation of prostatic acid phosphatase. Biochemistry 2001 40 15341-15348. 

Takayama TK, Carter CA, Deng T. Activation of prostate-specific antigen precursor (pro-PSA) by prostin, a novel human prostatic serine protease identified by degenerate PCR. Biochemistry 2001 40 1679-1687. 

Phage libraries have also been used to study the substrate specificity of enzymes by finding an improved artificial substrate. Coombs et al. (69) reported the detailed assessment of specificity for a serine protease belonging to the a-chymotrypsin family, the prostate specific antigen (PSA). They used both substrate optimization by singlepoint mutations and phage display libraries. The sequence of the 14-member substrate 10.2 (70) was used to start the iterative optimization process (Fig. 10.11) in which substitution or exchange of the PI, P2, or P2 residues increased the substrate affinity... 

Other enzymes are also useful indices of liver pathology. Serum alkaline phosphatase is often a useful indicator of liver and bone disease. The alkaline phosphatases are a diverse group of enzymes that catalyze reactions in which a phosphate is removed from a phosphate ester, especially at an alkaline pH. Physicians don t care about this. They do care that serum alkaline phosphatase levels often rise with bone breakdown (as in tumor infiltration) and in liver disease, especially where tliere is obstruction of the bile duct. Acid phosphatase is particularly rich in the prostate. A rise in its serum levels provides a test as to the presence of prostate carcinoma. This test has largely been replaced by assay for Prostate Specific Antigen (PSA), a serine protease that is elevated in prostatic carcinoma. 

Prostate-Specific Antigen (PSA) PSA is a serine protease that is present extracellularly in prostate cancers. PSA is inhibited in the bloodstream. As a result,... 

With few exceptions, an increase in the activity or mass of an enzyme or isoenzyme is not specific or sensitive enough to be used for identifying the type of cancer or the specific organ involvement. An exception is PSA. PSA has mild protease activity and amino acid sequence homology with serine protease of the kallikrein family.It is expressed by normal, benign, hyperplastic, and cancerous prostate glands and minimally by other tissue. Until the application of PSA as a marker for prostate cancer, tumor enzymes had lost most of their popularity for use as cancer markers. Enzymes were used historically as tumor markers before the discovery of oncofetal antigens and the advent of monoclonal antibodies. The abnormalities of enzymes as a marker for cancer are either the expression of the fetal form of the enzyme (isozyme) or the ectopic production of enzymes. 

Many studies show that the use of PCR-based molecular methods to amplify PSA-mRNA as molecular marker offer a sensitive assay for the detection of extraprostatic PSA synthesizing cells suitable for monitoring and detection of micrometastases and circulating tumor cells originated from prostatic carcinoma. The use of PSA as a molecular target proved to be more sensitive than the amplification of other prostate-specific tissue markers like prostate-specific membrane antigen (PSMA) or human glandular kallikrien (a member of the kallikrien family of serine proteases with trypsin like activity). 

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