In this study, the effect of the reducing sugar glyceraldehyde 3-phosphate on protein/DNA interaction has been investigated. Treatment with glyceraldehyde 3-phosphate of oligonucleotides recognized by various transcription factors severely inhibits protein binding. The inhibitory effect is time and dose-dependent. Treatment with glyceraldehyde 3-phosphate of the homeodomain protein TTF-1 HD has also an inhibitory effect on the interaction with DNA, again in a time and dose-dependent manner. These "in vitro" effects could have "in vivo" counterparts and therefore contribute to molecular alterations observed either when intracellular protein are exposed to high doses of reducing sugars (i.e. in diabetes) or after a long time exposure (i.e. in Gzero-arrested cells during aging).