Single-molecule
measurements of biomaterials bring novel insights
into cellular events. For almost all of these events, post-translational
modifications (PTMs), which alter the properties of proteins through
their chemical modifications, constitute essential regulatory mechanisms.
However, suitable single-molecule methodology to study PTMs is very
limited. Here we show single-molecule detection of peptide phosphorylation,
an archetypal PTM, based on electrical measurements. We found that
the phosphate group stably bridges a nanogap between metal electrodes
and exhibited high electrical conductance, which enables specific
single-molecule detection of peptide phosphorylation. The present
methodology paves the way to single-molecule studies of PTMs, such
as single-molecule kinetics for enzymatic modification of proteins
as shown here.