Abstract
Geminal bisphosphonates can be used for a variety of purposes in human disease including reduction of bone resorption in osteoporosis, treatment of fractures associated with malignancies of the prostate, breast, and lung, and direct anticancer activity against bone marrow derived malignancies. Previous research led to identification of some novel isoprenoid bisphosphonates that inhibit geranylgeranyl pyrophosphate (GGPP) synthesis and diminish protein geranylgeranylation. Described here is the synthesis of fluorescent anthranilate analogues of the most active isoprenoid bisphosphonates and examine their ability to impact post-translational processing of the small GTPases Ras, Rap1a, and Rab6. Similar to their non-fluorescent counterparts, some of these fluorescent isoprenoid bisphosphonates diminish protein geranylgeranylation. Their biological activity and fluorescent character suggest that they may be useful in studies of bisphosphonate localization both in cultured cells and in whole organisms.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1959-1966 |
| Number of pages | 8 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 15 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 1 2007 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
Cite this
}
Synthesis of fluorescently tagged isoprenoid bisphosphonates that inhibit protein geranylgeranylation. / Maalouf, Mona A.; Wiemer, Andrew J.; Kuder, Craig H.; Hohl, Raymond J.; Wiemer, David F.
In: Bioorganic and Medicinal Chemistry, Vol. 15, No. 5, 01.03.2007, p. 1959-1966.Research output: Contribution to journal › Article
TY - JOUR
T1 - Synthesis of fluorescently tagged isoprenoid bisphosphonates that inhibit protein geranylgeranylation
AU - Maalouf, Mona A.
AU - Wiemer, Andrew J.
AU - Kuder, Craig H.
AU - Hohl, Raymond J.
AU - Wiemer, David F.
PY - 2007/3/1
Y1 - 2007/3/1
N2 - Geminal bisphosphonates can be used for a variety of purposes in human disease including reduction of bone resorption in osteoporosis, treatment of fractures associated with malignancies of the prostate, breast, and lung, and direct anticancer activity against bone marrow derived malignancies. Previous research led to identification of some novel isoprenoid bisphosphonates that inhibit geranylgeranyl pyrophosphate (GGPP) synthesis and diminish protein geranylgeranylation. Described here is the synthesis of fluorescent anthranilate analogues of the most active isoprenoid bisphosphonates and examine their ability to impact post-translational processing of the small GTPases Ras, Rap1a, and Rab6. Similar to their non-fluorescent counterparts, some of these fluorescent isoprenoid bisphosphonates diminish protein geranylgeranylation. Their biological activity and fluorescent character suggest that they may be useful in studies of bisphosphonate localization both in cultured cells and in whole organisms.
AB - Geminal bisphosphonates can be used for a variety of purposes in human disease including reduction of bone resorption in osteoporosis, treatment of fractures associated with malignancies of the prostate, breast, and lung, and direct anticancer activity against bone marrow derived malignancies. Previous research led to identification of some novel isoprenoid bisphosphonates that inhibit geranylgeranyl pyrophosphate (GGPP) synthesis and diminish protein geranylgeranylation. Described here is the synthesis of fluorescent anthranilate analogues of the most active isoprenoid bisphosphonates and examine their ability to impact post-translational processing of the small GTPases Ras, Rap1a, and Rab6. Similar to their non-fluorescent counterparts, some of these fluorescent isoprenoid bisphosphonates diminish protein geranylgeranylation. Their biological activity and fluorescent character suggest that they may be useful in studies of bisphosphonate localization both in cultured cells and in whole organisms.
UR - http://www.scopus.com/inward/record.url?scp=33846615517&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846615517&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2007.01.002
DO - 10.1016/j.bmc.2007.01.002
M3 - Article
C2 - 17254791
AN - SCOPUS:33846615517
VL - 15
SP - 1959
EP - 1966
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 5
ER -