A nanografting method was used to fabricate well packed ss-DNA nanopatches within a SAM of inert thiols on gold surfaces. Accurate height and compressibility measurements of the nanopatches before and after hybridization allowed reliable, sensitive, and label-free detection of hybridization. Side-by-side comparison of SAM and nanografted DNA-monolayers shows that the latter display higher hybridization efficiencies. A p -aminophenol modified carbon paste electrode ( p -APMCPE) was constructed for the determination of 6-thioguanine (6-TG). The cyclic voltammogram showed that the electrocatalytic oxidation of 6-TG occurs at the surface of p -APMCPE. The kinetic parameters such as electron transfer coefficient and rate constant were determined for the chemical reaction between 6-TG and p -aminophenol. A sensitive square wave voltammetry (SWV) method was used for the determination of 6-TG at the surface of mercury electrode. The interaction of 6-TG with ds-DNA resulted in the amplification of SWV response. SWV and UV–vis studies showed that the intercalation of 6-TG into ds-DNA would be the probable reason for the observed behavior. A sensitive differential pulse voltammetry (DPV) procedure was introduced for the determination of amiloride at a ds-DNA-modified pencil graphite electrode (PGE). The decrease in the oxidation signal of guanine and adenine was obtained before and after interaction with amiloride. UV–vis measurements combined with DPV showed that the most plausible mechanism for the interaction of amiloride and ds-DNA would be the intercalation.