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. Author manuscript; available in PMC: 2013 Jun 22.
Published in final edited form as: Chem Biol. 2012 Jun 22;19(6):721–730. doi: 10.1016/j.chembiol.2012.04.012

Figure 1. Proposed HGXPRT transition state structures and transition state analogs of PfHGXPRT.

Figure 1

(a) Proposed transition state based on the transition states of enzymes catalyzing similar reactions. Li et al (1999) proposed this transition state for HG(X)PRT with a protonated N7 and oxocarbenium ion formation at C1′. (b) Immucillin-H 5′-phosphate was designed as a mimic of this proposed transition state. The acyclic Immucillin phosphonates (AIPs) 2 and 3 are powerful and selective inhibitors of PfHGXPRT. The AIPs maintain key features of Immucillin-H 5’-phosphate including the 9-deazahypoxanthine nucleobase, ribocationic nitrogen, and a phosphonate group. (c) The inhibition constants for 2 and 3 with PfHGXPRT and human HGPRT.