N-hydroxyurea--a versatile zinc binding function in the design of metalloenzyme inhibitors.

Article Details

Citation

Temperini C, Innocenti A, Scozzafava A, Supuran CT

N-hydroxyurea--a versatile zinc binding function in the design of metalloenzyme inhibitors.

Bioorg Med Chem Lett. 2006 Aug 15;16(16):4316-20. Epub 2006 Jun 12.

PubMed ID
16759856 [ View in PubMed
]
Abstract

N-Hydroxyurea binds both to carbonic anhydrase (CA) and to matrix metalloproteinases (MMPs). X-ray crystallography showed N-hydroxyurea to bind in a bidentate mode by means of the oxygen and nitrogen atoms of the NHOH moiety to the Zn(II) ion of CA, participating in a network of hydrogen bonds with a water molecule and Thr199. A derivatized N-hydroxyurea showed low-micromolar affinity for several CAs. This simple zinc binding function may be exploited for obtaining potent metalloenzyme inhibitors, due to its versatility of binding to the metal ion present in the active site of such enzymes.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Carbonic anhydrase 2P00918Details