An image contrast agent selectively activated by prostate specific antigen.

Graham B Jones; Curtis F Crasto; Jude E Mathews; Longfei Xie; Miguel O Mitchell; Ahmed El-Shafey; Anthony V D'Amico; Glenn J Bubley

doi:10.1016/j.bmc.2005.08.015

PubMed · 16185875

An image contrast agent selectively activated by prostate specific antigen.

Graham B Jones·Curtis F Crasto·Jude E Mathews·Longfei Xie·Miguel O Mitchell·Ahmed El-Shafey·Anthony V D'Amico·Glenn J Bubley

View original source ↗Export metadata ↓

Abstract

A family of image contrast agent conjugates designed to undergo enzymatic activation has been synthesized. The agents underwent activation both with enzymatically active prostate specific antigen (PSA) and alpha-chymotrypsin, releasing free fluorophore via cleavage of a three-component system. A hexapeptide derivative showed exclusive activation by PSA and constitutes a method for tracking PSA activity in vitro.

Explore related subjects

Chymotrypsin Contrast Media Enzyme Activation Magnetic Resonance Spectroscopy Prostate-Specific Antigen Spectrometry, Mass, Electrospray Ionization Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Graham B Jones, Curtis F Crasto, Jude E Mathews, Longfei Xie, Miguel O Mitchell, Ahmed El-Shafey, Anthony V D'Amico, Glenn J Bubley. 2005-09-26. An image contrast agent selectively activated by prostate specific antigen.. https://doi.org/10.1016/j.bmc.2005.08.015

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Crosslinked enzyme aggregates in hierarchically-ordered mesoporous silica: a simple and effective method for enzyme stabilization.

alpha-chymotrypsin (CT) and lipase (LP) were immobilized in hierarchically-ordered mesocellular mesoporous silica (HMMS) in a simple but effective way for the enzyme stabilization, which was achieved by the enzyme adsorption followed by glutaraldehyde (GA) crosslinking. This resulted in the formation of nanometer scale crosslinked enzyme aggregates (CLEAs) entrapped in the mesocellular pores of HMMS (37 nm), which did not leach out of HMMS through narrow mesoporous channels (13 nm). CLEA of alpha-chymotrypsin (CLEA-CT) in HMMS showed a high enzyme loading capacity and significantly increased enzyme stability. No activity decrease of CLEA-CT was observed for 2 weeks under even rigorously shaking condition, while adsorbed CT in HMMS and free CT showed a rapid inactivation due to the enzyme leaching and presumably autolysis, respectively. With the CLEA-CT in HMMS, however, there was no tryptic digestion observed suggesting that the CLEA-CT is not susceptible to autolysis. Moreover, CLEA of lipase (CLEA-LP) in HMMS retained 30% specific activity of free lipase with greatly enhanced stability. This work demonstrates that HMMS can be efficiently employed as host materials for enzyme immobilization leading to highly enhanced stability of the immobilized enzymes with high enzyme loading and activity.

Chymotrypsin↗

PubMed2006

Protease-catalyzed synthesis of the tripeptide CCK(26-28), a fragment of CCK-8.

Two enzymatically synthetic strategies of the tripeptide derivative PhAc-Asp(OMe)-Tyr-Met-OAl are reported. The second strategy gains the advantage of more economical starting materials, less reaction steps and a higher overall isolated yield of this tripeptide fragment over the first strategy. The effect of the acyl-donor ester concentration and structure, the C-alpha protecting group of the nucleophile, reaction media, enzyme and the carrier on the tripeptide derivative synthesis were studied. This tripeptide selected is a fragment of the cholecystokinin C-terminal octapeptide (CCK-8), a potential therapeutic agent in the control of gastrointestinal function and also a drug candidate for the treatment of epilepsy.

Chymotrypsin↗

PubMed2006

Novel beta-lactam derivatives: potent and selective inhibitors of the chymotrypsin-like activity of the human 20S proteasome.

A series of beta-lactam derivatives has been designed and synthesized to inhibit the chymotrypsin-like activity of the human 20S proteasome. The most potent compounds of this new structural class of beta-subunit selective 20S proteasome inhibitors exhibit IC50 values in the low-nanomolar range and show good selectivity over the trypsin-like and post-glutamyl-peptide hydrolytic activities of the enzyme.

Chymotrypsin↗