Telomeric C-strand sequences form non-Watson-Crick base-paired structu
res in supercoiled plasmids and in oligonucleotides at low pH. Here we
examine oligonucleotides composed of 2 or 4 repeats of the human telo
meric C-strand sequence d(CCCTAA)(n). At low pH, the 2-repeat molecule
forms a dimer which exhibits H1'-H1' nuclear Overhauser effects (NOEs
) between stacked C.C+ base pairs. These NOEs ave characteristic of th
e i-motif, which is a tetraplex composed of two intercalated C.C+ dupl
exes. The 4-repeat molecule forms an intramolecular monomeric structur
e at low pH, suggesting that four contiguous cytosine tracts fold into
a C.C+ intercalated tetraplex. These unusual structures may be releva
nt to the formation of guanine tetraplexes by complementary G-rich seq
uences. They may also provide a general mechanism for self-recognition
by nucleic acids.