Analysis of the S(2) subsite specificities of the recombinant cysteine proteinases CPB of Leishmania mexicana, and cruzain of Trypanosoma cruzi, using fluorescent substrates containing non-natural basic amino acids

Molecular and Biochemical Parasitology
L C AlvesMaria A Juliano

Abstract

We have explored the specificity of the S(2) subsite of recombinant cysteine proteinases from Leishmania mexicana (CPB2.8 Delta CTE) and from Trypanosoma cruzi (cruzain) employing a series of fluorogenic substrates based on the peptide Bz-F-R-MCA, in which Bz is the benzoyl group and the Phe residue has been substituted for by Arg, His and non-natural basic amino acids that combine a basic group with an aromatic or hydrophobic group at the side chain: 4-aminomethyl-phenylalanine (Amf), 4-guanidine phenylalanine (Gnf), 4-aminomethyl-N-isopropyl-phenylalanine (Iaf), 3-pyridyl-alanine (Pya), 4-piperidinyl-alanine (Ppa), 4-aminomethyl-cyclohexyl-alanine (Ama), and 4-aminocyclohexyl-alanine (Aca). Bz-F-R-MCA was hydrolyzed well by CPB2.8 Delta CTE and cruzain, but all the substitutions of Phe resulted in less susceptible substrates for the two enzymes. CPB2.8 Delta CTE has a restricted specificity to hydrophobic side chains as with cathepsin L. However, the peptides with the residues Amf and Ama presented higher affinity to CPB2.8 Delta CTE, and the latter was an inhibitor of the enzyme. Although, cruzain accepts basic as well as hydrophobic residues at the S(2) subsite, it is more restrictive than cathepsin B and no inhibitor was f...Continue Reading

References

Nov 24, 1976·Journal of the American Chemical Society·A C PaivaP Boschcov
Dec 1, 1992·Molecular and Biochemical Parasitology·A P LimaR Ménard
Jul 1, 1992·FEMS Microbiology Letters·C D Robertson, G H Coombs
Nov 1, 1990·Molecular and Biochemical Parasitology·A C MurtaJ Scharfstein
Sep 1, 1990·Molecular and Biochemical Parasitology·C D Robertson, G H Coombs
Oct 1, 1984·The Biochemical Journal·M J Nicklin, A J Barrett
Jun 2, 1980·FEBS Letters·H J KärgelJ Langner
Jul 1, 1981·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·W T Stauber, S H Ong
May 1, 1994·The Journal of Eukaryotic Microbiology·P A BatesG H Coombs
Jun 11, 1996·Proceedings of the National Academy of Sciences of the United States of America·J C MottramG H Coombs
Jun 24, 1996·FEBS Letters·F AuthierJ J Bergeron
Aug 1, 1997·Protein Science : a Publication of the Protein Society·S A GillmorR J Fletterick
Jul 20, 1999·Annual Review of Biophysics and Biomolecular Structure·M E McGrath
Apr 6, 2000·The Biochemical Journal·S J SandersonG H Coombs
May 18, 2001·Molecular and Biochemical Parasitology·L C AlvesM A Juliano
Jul 21, 2001·Molecular and Biochemical Parasitology·L C AlvesM A Juliano
Aug 1, 1961·The Biochemical Journal·G N WILKINSON
Aug 17, 2010·Biochemical Pharmacology·S BienH K Kroemer
Jul 1, 1978·Meat Science·B Venugopal, M E Bailey

❮ Previous
Next ❯

Citations

Jul 16, 2013·European Journal of Medicinal Chemistry·Lorena BlauChung Man Chin
Jul 23, 2002·Current Opinion in Chemical Biology·Alejandro Alvarez Hernandez, William R Roush
Jan 8, 2013·Journal of Agricultural and Food Chemistry·Ratnasiri MaddumageRoss G Atkinson
Dec 7, 2011·Antimicrobial Agents and Chemotherapy·Marie SchaefferGraham H Coombs
Mar 31, 2012·Expert Opinion on Drug Discovery·Deborah A Nicoll-Griffith
May 10, 2012·Molecular and Biochemical Parasitology·Elide E CaroselliLuiz Juliano
Apr 12, 2016·Journal of Biomolecular Structure & Dynamics·Drielli G VitalGustavo H G Trossini
Sep 10, 2009·The Journal of Eukaryotic Microbiology·Claudia M D'Avila-LevyMarta H Branquinha
Dec 25, 2009·Journal of Enzyme Inhibition and Medicinal Chemistry·Gustavo H G TrossiniElizabeth Igne Ferreira
Jul 31, 2019·Journal of Medicinal Chemistry·Lorenzo CianniCarlos A Montanari

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.