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Structural characterization of P1'-diversified urea-based inhibitors of glutamate carboxypeptidase II.

Abstract：

:Urea-based inhibitors of human glutamate carboxypeptidase II (GCPII) have advanced into clinical trials for imaging metastatic prostate cancer. In parallel efforts, agents with increased lipophilicity have been designed and evaluated for targeting GCPII residing within the neuraxis. Here we report the structural and computational characterization of six complexes between GCPII and P1'-diversified urea-based inhibitors that have the C-terminal glutamate replaced by more hydrophobic moieties. The X-ray structures are complemented by quantum mechanics calculations that provide a quantitative insight into the GCPII/inhibitor interactions. These data can be used for the rational design of novel glutamate-free GCPII inhibitors with tailored physicochemical properties.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Pavlicek J,Ptacek J,Cerny J,Byun Y,Skultetyova L,Pomper MG,Lubkowski J,Barinka C

doi

10.1016/j.bmcl.2014.03.066

subject

Has Abstract

pub_date

2014-05-15 00:00:00

pages

2340-5

issue

10

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(14)00293-5

journal_volume

24

pub_type

杂志文章

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