Details

Autor(en) / Beteiligte

• Johayem, Anass
• Raić-Malić, Silvana
• Lazzati, Katia
• Schubiger, Pius A.
• Scapozza, Leonardo
• Ametamey, Simon M.

Titel

Synthesis and Characterization of a C(6) Nucleoside Analogue for the in vivo Imaging of the Gene Expression of Herpes Simplex Virus Type-1 Thymidine Kinase (HSV1 TK)

Ist Teil von

• Chemistry & biodiversity, 2006-03, Vol.3 (3), p.274-283

Ort / Verlag

Zürich: WILEY-VCH Verlag

Erscheinungsjahr

2006

Quelle

Wiley Online Library

Beschreibungen/Notizen

• The synthesis and biological evaluation of ‘6‐(1,3‐dihydroxyisobutyl)thymine’ (DHBT; 1), which corresponds to 6‐[3‐hydroxy‐2‐(hydroxymethyl)propyl]‐5‐methylpyrimidine‐2,4(1H,3H)‐dione, is reported. DHBT (1) was designed as a new substrate for herpes simplex virus type‐1 thymidine kinase (HSV1 TK). The compound was found to be exclusively phosphorylated by HSV1 TK, and to exhibit good binding affinity (Ki = 35.3±1.3 μM). Cell‐proliferation assays with HSV1‐TK‐transduced human osteosarcoma cells (143B‐TK+‐HSV1‐WT) and with both human‐thymidine‐kinase‐1‐negative (143B‐TK−) and non‐transduced parental (MG‐63) cells indicate that 1 is less cytotoxic than the standard drug Ganciclovir. Thus, DHBT (1) represents a promising precursor of a nontoxic reporter probe for the monitoring of HSV1 TK gene expression by means of positron‐emission tomography (PET).