The easily accessible C-nucleoside 2-amino-5-(2‘-deoxy-β-d-ribofuranosyl)pyridine (P) and its 3-methyl (^MeP) and 2‘-O-methyl (P_OMe) derivatives were synthesized and incorporated as protonated cytidine equivalents in homopyrimidine oligodeoxynucleotides. T_m measurements indicate that oligonucleotides containing P or ^MeP have a higher affinity to double-stranded DNA over the pH range of 6−8 than 5-methylcytidine (^MeC) containing oligonucleotides. This increase in stability is most pronounced above pH 7.0. The average increase in T_m/modification for the dissociation of oligonucleotide d(TTTTT^MePT^MePT^MePT^MePT^MePT) from a 21-mer target duplex at pH 7.5 is 2.3 °C relative to oligonucleotide d(TTTTT^MeCT^MeCT^MeCT^MeCT^MeCT). The pH dependence and sequence composition effects are much less pronounced for ^MeP (and also P) containing oligonucleotides than for ^MeC containing ones. While oligonucleotide d(TTT^MeC^MeC^MeC^MeCTTTT^MeCTTT) shows no longer any affinity to the target duplex above pH 6.5, oligonucleotide d(TTT^MeP^MeP^MeP^MePTTTT^MePTTT) displays preserved binding with a T_m of 32.5 °C at pH 7.0 and even binds with a T_m of 23.3 °C at pH 8.0. Oligonucleotides containing P_OMe show distinctly less stable triple helices. The average decrease in T_m/modification for oligonucleotide d(TTTTTP_OMeTP_OMeTP_OMeTP_OMeTP_OMeT) at pH 6.5 is 6.7 °C relative to the ^MeC containing oligonucleotide. DNase I footprint titration experiments indicate that d(TTTTT^MePT^MePT^MePT^MePT^MePT) binds not only five times stronger to a 229 base pair DNA fragment than d(TTTTT^MeCT^MeCT^MeCT^MeCT^MeCT) but also with higher selectivity. UV-melting experiments show that duplexes of d(TTTTTCTXTCTCTCT) (where X = P, ^MeP, or P_OMe) with their antiparallel Watson−Crick complement are dramatically less stable (ΔT_m < −12 °C) at pH 8.0 than the corresponding natural duplex. Thus the new bases P and ^MeP show Hoogsteen specific pairing behavior.