Improving the Specificity of the Prostate-Specific Antigen Substrate Glutaryl-Hyp-Ala-Ser-Chg-Gln as a Promoiety

Chemical Biology & Drug Design
Herve Aloysius, Longqin Hu

Abstract

To develop PSA peptide substrates with improved specificity and plasma stability from the known substrate sequence glutaryl-Hyp-Ala-Ser-Chg-Gln, systematic replacements of the N-terminal segment with D-retro-inverso-peptides were performed with the incorporation of 7-amino-4-methylcoumarin (7-AMC) after Gln for convenient fluorometric determination and ranking of the PSA substrate activity. The D-retro-inverso-peptide conjugates with P2-P5 D-amino acid substitutions were moderate but poorer PSA substrates as compared to the original peptide, suggesting that inversion of the amide bonds and/or incorporation of the additional atom as in the urea linker adversely affected PSA binding. However, P5 substitution of Hyp with Ser showed significant improvements in PSA cleavage rate; the resulting AMC conjugate, glutaryl-Ser-Ala-Ser-Chg-Gln-AMC (11), exhibited the fastest PSA cleavage rate of 351 pmol/min/100 nmol PSA. In addition, GABA←mGly-Ala-Ser-Chg-Gln-AMC (conjugate 6) was the second best PSA substrate and released 7-AMC at a rate of 225 pmol/min/100 nmol PSA as compared to 171 pmol/min/100 nmol PSA for the control conjugate glutaryl-Hyp-Ala-Ser-Chg-Gln-AMC. Incubations of selected AMC conjugates with mouse and human plasma reveal...Continue Reading

References

Jan 1, 1995·Journal of Clinical Laboratory Analysis·M LevesqueE P Diamandis
Jan 1, 1995·Scandinavian Journal of Clinical and Laboratory Investigation. Supplementum·E P Diamandis
Jun 1, 1996·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·I F TannockK C Murphy
Jun 1, 1996·Hematology/oncology Clinics of North America·M Robson, N Dawson
Nov 4, 2000·Expert Opinion on Investigational Drugs·L R Kelland
Mar 29, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Robert S DiPaolaSiu-Long Yao
Dec 7, 2002·The Journal of Organic Chemistry·Rimma ShelkovArtem Melman
May 30, 2006·Clinical Genitourinary Cancer·Robert J Amato, Harmeet Sarao
Dec 12, 2007·Handbook of Experimental Pharmacology·A Jakobovits
Jan 22, 2008·British Journal of Pharmacology·J M AtkinsonJ H Gill
Feb 28, 2008·The Cancer Journal·Shi-Ming Tu, Sue-Hwa Lin
May 29, 2008·British Journal of Cancer·R E Coleman
Jul 17, 2008·Expert Opinion on Pharmacotherapy·Sara De Dosso, Dominik R Berthold
Mar 9, 2012·Theranostics·Ki Young ChoiXiaoyuan Chen
Apr 6, 2012·World Journal of Urology·Otis W Brawley
Jan 9, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Mar 19, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Dec 23, 2014·Medicinal Research Reviews·Herve Aloysius, Longqin Hu

❮ 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.

Related Papers

Progrès en urologie : journal de l'Association française d'urologie et de la Société française d'urologie
R Boissier
© 2021 Meta ULC. All rights reserved