Non‐Hydrolysable Analogues of Cyclic and Branched Condensed Phosphates: Chemistry and Chemical Proteomics

Abstract

AbstractStudies into the biology of condensed phosphates almost exclusively cover linear polyphosphates. However, there is evidence for the presence of cyclic polyphosphates (metaphosphates) in organisms and for enzymatic digestion of branched phosphates (ultraphosphates) with alkaline phosphatase. Further research of non‐linear condensed phosphates in biology would profit from interactome data of such molecules, however, their stability in biological media is limited. Here we present syntheses of modified, non‐hydrolysable analogues of cyclic and branched condensed phosphates, called meta‐ and ultraphosphonates, and their application in a chemical proteomics approach using yeast cell extracts. We identify putative interactors with overlapping hits for structurally related capture compounds underlining the quality of our results. The datasets serve as starting point to study the biological relevance and functions of meta‐ and ultraphosphates. In addition, we examine the reactivity of meta‐ and ultraphosphonates with implications for their “hydrolysable” analogues: Efforts to increase the ring‐sizes of meta‐ or cyclic ultraphosphonates revealed a strong preference to form trimetaphosphate‐analogue structures by cyclization and/or ring‐contraction. Using carbodiimides for condensation, the so far inaccessible dianhydro product of ultraphosphonate, corresponding to P4O112−, was selectively obtained and then ring‐opened by different nucleophiles yielding modified cyclic ultraphosphonates.