Structural Requirements for the Enzymatic Deamination of Cytosine Nucleosides

✍ Scribed by W. Kreis; K. A. Watanabe; J. J. Fox

• Publisher: John Wiley and Sons
• Year: 1978
• Tongue: German
• Weight: 373 KB
• Volume: 61
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19780610310

✦ Synopsis

Abstract

Thirty‐three 1‐β‐D‐pentofuranosylcytosine nucleosides were examined as substrates of crude cytidine deaminase from mouse kidney. In addition to previous observations of structural features in substrates required for enzymatic deamination [e.g., a free 3′‐hydroxyl in the ‘down’ ribo (arabino)configuration] we find that: modification of the aglycon by substitution of a fluorine atom at C(5) results in a several‐fold increase in the deamination velocity relative to cytidine whereas insertion of a methyl group at C(5) decreases the deamination velocity. This decrease is even more pronounced when a methyl group is substituted at C(6).

Though xylosylcytosine and 3′‐deoxy‐3′‐fluoro‐xylo‐C are not substrates for this deaminase, those xylofuranosylcytosines bearing good leaving groups (e.g., bromo, mesyloxy, or tosyloxy) at C(3′) are deaminated with substantial deamination velocities. This is probably due to a prior chemical reaction leading to arabino nucleosides bearing a free ‘down’ 3′‐hydroxyl.

A different situation is obtained with arabino nucleosides. Though ara‐C and 2′‐deoxy‐2′‐fluoro‐ara‐C are substrates for this deaminase, substitution of bulky groups (e.g., chloro, bromo, or mesyloxy) at C(2′) substantially decreases the susceptibility to deamination. An hypothesis is offered to explain these differences between xylo‐and arabino‐cytosines.

The presence of a free hydroxyl group at position 5′ is not essential for enzymatic deamination.