Prolidase, a potential enzyme target for melanoma: design of proline-containing dipeptide-like prodrugs.

  title={Prolidase, a potential enzyme target for melanoma: design of proline-containing dipeptide-like prodrugs.},
  author={Sachin Mittal and Xueqin Song and Balvinder S. Vig and Christopher P. Landowski and Insook Kim and John M. Hilfinger and Gordon L Amidon},
  journal={Molecular pharmaceutics},
  volume={2 1},
Bioinformatics tools such as Perl, Visual Basic, Cluster, and TreeView were used to analyze public gene expression databases in order to identify potential enzyme targets for prodrug strategies. The analyses indicated that prolidase might be a desirable enzyme target based on its differential expression in melanoma cancer cell lines and its high substrate specificity for dipeptides containing proline at the carboxy terminus. RT-PCR expression of prolidase and hydrolytic activity against N… 

Dipeptidyl Peptidase IV as a Potential Target for Selective Prodrug Activation and Chemotherapeutic Action in Cancers

The results demonstrate the great potential to exploit DPPIV as a prodrug activating enzyme for efficient chemotherapeutic drug targeting.

Proline Prodrug of Melphalan Targeted to Prolidase, a Prodrug Activating Enzyme Overexpressed in Melanoma

Prophalan-L, a stable prodrug of melphalan, exhibits potential for efficiently targeting melanoma with reduced systemic toxicity and corroborates the specificity of prophAlan-L activation by Prolidase as well as prolidase-targeted cytotoxicity of proPHalan- L in cancer cell lines.

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Results indicate the proline-linked nitrosoureas (1-4), represent multifunctional inhibitors of breast cancer cell growth and metabolism.

Prolidase function in proline metabolism and its medical and biotechnological applications

The many in vivo functions of procaryotic and eucaryotic prolidases, as well as the most recent advances in therapeutic and biotechnological application of prolidase are discussed.

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Biochemical characterization of two thermostable prolidases identified in the genome of Pyrococcus horikoshii shows they have higher catalytic activities over a broader pH range, higher affinity for metal and are more stable compared to P. furiosus prolidase.

Current Understanding of the Emerging Role of Prolidase in Cellular Metabolism

An in-depth understanding of prolidase as a dipeptidase and protein regulating the function of key biomolecules in cellular metabolism is provided.

Nucleoside Ester Prodrug Substrate Specificity of Liver Carboxylesterase

Initial hydrolysis rates are relatively low for prodrugs with isoleucyl, aspartyl, and lysyl promoieties for both enzymes compared with those with phenylalanyl, valyl, prolyl, and leucyl progroups, suggesting prolonged systemic disposition of the nucleoside analogs for improved therapeutic action.

Human prolidase and prolidase deficiency: an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations

Recombinant human prolidase was produced in prokaryotic and eukaryotic hosts with biochemical properties similar to the endogenous enzyme and represents a valid tool both to better understand the structure and biological function of the enzyme and to develop an enzyme replacement therapy for the prolid enzyme deficiency (PD).

Crystal structure of a novel prolidase from Deinococcus radiodurans identifies new subfamily of bacterial prolidases

The structural, mutational, and molecular dynamics simulation analyses show that the conserved Arg46 of N‐terminal domain is important for the dipeptide selectivity of XPPdr, thus identifying a new subfamily of bacterial prolidases.