Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Optimization of an albumin-binding prodrug of doxorubicin that is cleaved by prostate-specific antigen
ACS Medicinal Chemistry Letters, Volume 1, No. 5, Year 2010
Notification
URL copied to clipboard!
Description
We have developed a novel albumin-binding prodrug of doxorubicin that incorporates p-aminobenzyloxycarbonyl (PABC) as a 1,6 self-immolative spacer in addition to the heptapeptide, Arg-Ser-Ser-Tyr-Tyr-Ser-Leu, as a substrate for the prostate-specific antigen (PSA) that is overexpressed in prostate carcinoma and represents a molecular target for selectively releasing an anticancer agent from a prodrug formulation. The prodrug exhibited good water solubility and was bound rapidly to the cysteine-34 position of human serum albumin. Incubation studies with PSA demonstrated that the albumin-bound form of the prodrug was cleaved rapidly at the P1?P1? scissile bond, releasing H-Ser-Leu-PABC-DOXO, which was further degraded to release doxorubicin as a final cleavage product within a few hours in prostate tumor tissue homogenates as well as in PSA-positive LNCaP LN cell lysates. Moreover, our prodrug exhibited antiproliferative activity in a low micromolar range against a PSA-expressing prostate cancer cell line (LNCaP). © 2010 American Chemical Society.
Authors & Co-Authors
Elsadek, Bakheet E.M.
Germany, Freiberg am Neckar
Klinik Für Tumorbiologie
Egypt, Cairo
Faculty of Pharmacy
Graeser, Ralph
Germany, Freiburg Im Breisgau
Proqinase Gmbh
Warnecke, André
Germany, Freiberg am Neckar
Klinik Für Tumorbiologie
Unger, Clemens
Germany, Freiberg am Neckar
Klinik Für Tumorbiologie
Saleem, Tahia Hashem
Egypt, Asyut
Faculty of Medicine
El-Melegy, Nagla Taha
Egypt, Asyut
Faculty of Medicine
Madkor, Hafez R.
Egypt, Cairo
Faculty of Pharmacy
Kratz, Felix
Germany, Freiberg am Neckar
Klinik Für Tumorbiologie
Statistics
Citations: 38
Authors: 8
Affiliations: 4
Identifiers
Doi:
10.1021/ml100060m
e-ISSN:
19485875
Research Areas
Cancer
Environmental