Chemistry of bifunctional photoprobes II. Chemical and photochemical modification of angiotensin converting enzyme inhibitors

Implications in the development of cardiac radionuclide imaging agents

Raghoottama S. Pandurangi, Przemyslaw Lusiak, Robert R. Kuntz, Yao Sun, Karl Weber

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The synthesis and biological activity of functionalized lisinopril, a potent angiotensin converting enzyme (ACE) inhibitor is described. Selective functionalization of lisinopril is achieved at the secondary amino position by a photochemical method, whereas esterfication of the carboxylic groups and modification at the primary amino group is achieved by chemical methods. Autoradiographic investigations using competitive 125I radioactive binding assays with the modified lisinopril reveal that the terminal amino group modification enhanced the binding to ACE, whereas the secondary amino group functionalization did not differ significantly from the binding properties of native lisinopril. However, esterification of the carboxyl groups reduced the inhibitory potentency from nM to μM. These results suggest that lisinopril can be derivatized with preservation of inhibition potency toward ACE. These modifications may find utility in the development of photoaffinity labeling agents for ACE or to incorporate bifunctional chelating agents carrying diagnostic radiometals for the development of cardiac imaging agents.

Original languageEnglish (US)
Pages (from-to)77-87
Number of pages11
JournalBioorganic Chemistry
Volume25
Issue number2
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

Fingerprint

Lisinopril
Angiotensin-Converting Enzyme Inhibitors
Radioisotopes
Radionuclide Imaging
Imaging techniques
Peptidyl-Dipeptidase A
Esterification
Chelating Agents
Bioactivity
Labeling
Assays

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

Cite this

Chemistry of bifunctional photoprobes II. Chemical and photochemical modification of angiotensin converting enzyme inhibitors : Implications in the development of cardiac radionuclide imaging agents. / Pandurangi, Raghoottama S.; Lusiak, Przemyslaw; Kuntz, Robert R.; Sun, Yao; Weber, Karl.

In: Bioorganic Chemistry, Vol. 25, No. 2, 01.01.1997, p. 77-87.

Research output: Contribution to journalArticle

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