AbstractROMPing with the ADAMs family: The sperm‐surface display of egg adhesion proteins was investigated using multivalent polymer sperm mimics. Ruthenium‐catalyzed ring opening metathesis polymerization (ROMP) was used to synthesize heterovalent polymers.magnified imageThe sperm proteins ADAM2 and ADAM3, members of the ADAM family of proteins, have been implicated in mammalian sperm–egg binding. However, elucidating their roles is complex because of the interdependence of ADAM protein expression in the testis. Hence, multivalent probes containing the three‐amino acid binding sequence of ADAM2, glutamate‐cysteine‐aspartate (ECD), and ADAM3, glutamine‐cysteine‐aspartate (QCD), were designed, synthesized, and tested to investigate gamete interactions. In this work, ECD polymer mimics were synthesized by ring‐opening metathesis polymerization with a faster initiating ruthenium catalyst than previously used. Polymers containing 100 copies of the ECD peptide mimic were found to be the best inhibitors of fertilization. The multivalent QCD polymers were also tested as inhibitors of fertilization. The structure‐activity profile was the same as ECD polymers, but the overall potency was lower. Both ECD and QCD polymers require the presence of β1 integrin to inhibit fertilization. Next, triblock ABA and ABC copolymers containing both ECD and QCD ligands were synthesized with 96 monomer spacers as their B blocks. Although these polymers had lower densities of ECD and QCD peptides, their potencies correlated with the potencies of their corresponding homopolymers. In addition, no synergy between ECD and QCD mimics was observed. All the data suggest that QCD and ECD bind to the same complex of proteins that includes β1 integrin.