Fmoc-protected hydrophilic amino acids were prepared and incorporated into peptide nucleic acid (FNA). N- and C-terminal modification of FNA did not affect its ability to hybridize to complementary nucleic acid targets as determined by dot blot, PNA-FISH and Tm experiments. The compounds allowed us to prepare several probes which were previously impossible to make, purify or use due to limited aqueous solubility or self-aggregation. (C) 1998 Elsevier Science Ltd. All rights reserved.