Abstract
Three isoprenoid diphosphate analogues of farnesyl diphosphate (FPP) where the diphosphate has been replaced by methylene diphosphonate and the negative charges masked by frangible pivaloyloxymethyl (POM) esters were prepared. Farnesyl methylenediphosphonate is a sub-micromolar substrate for protein farnesyl transferase. The tripivaloyloxymethyl esters of isoprenoid methylenediphosphonate have significantly increased lipophilicity and may act as important farnesyl diphosphate prodrugs.
| Original language | English |
|---|---|
| Pages (from-to) | 4979-4982 |
| Number of pages | 4 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 14 |
| Issue number | 19 |
| DOIs | |
| State | Published - Oct 4 2004 |
Bibliographical note
Funding Information:This work was supported in part by the Kentucky Lung Cancer Research Program (to H.P.S. and D.A.A.), the National Institutes of Health (GM66152-01 to H.P.S.), and the NMR instruments used in this work were obtained with support from NSF CRIF Grant No. CHE-9974810. We thank Dr. Carol Fierke and Jennifer Pickett for the gift of rat protein farnesyltransferase.
Funding
This work was supported in part by the Kentucky Lung Cancer Research Program (to H.P.S. and D.A.A.), the National Institutes of Health (GM66152-01 to H.P.S.), and the NMR instruments used in this work were obtained with support from NSF CRIF Grant No. CHE-9974810. We thank Dr. Carol Fierke and Jennifer Pickett for the gift of rat protein farnesyltransferase.
| Funders | Funder number |
|---|---|
| Kentucky Lung Cancer Research Program | |
| National Science Foundation (NSF) | CHE-9974810 |
| National Institutes of Health (NIH) | GM66152-01 |
| National Institute of General Medical Sciences | R01GM066152 |
Keywords
- Bisphosphonates
- Farnesylation
- Prodrugs
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry