Oligoamide strands that associate in a sequence-specific fashion into hydrogen-bonded duplexes in nonpolar solvents were converted into olefin- or disulfide-crosslinked duplexes in both nonpolar and highly polar media. For example, by incorporating trityl-protected thiol groups, which allows the reversible formation of disulfide bonds, into the oligoamide strands, only duplexes consisting of complementary hydrogen-bonding sequences were formed in aqueous solution as well as in methanol. The sequence-specific crosslinking of oligoamide strands were confirmed by MALDI-TOF, reverse-phase HPLC and by isolating a crosslinked duplex. Our study demonstrates that the sequence-specificity characteristic of multiply hydrogen-bonded systems can be extended into competitive as well as nonpolar media through the interplay of H-bonding and reversible covalent interactions, based on which a new class of molecular associating and ligating units that are compatible with both polar and nonpolar environments can be conveniently obtained. Specifically, dynamic covalent block copolymers are easily generated based on these associating units.