Chemical Synthesis of NICOL, A Coligand Secreted Protein Mediating Mammalian Male Reproductive Tract Trans‐luminal Signaling

The NELL2-interacting cofactor for lumicrine signaling (NICOL) is a small protein which forms a complex with the neural epidermal growth factor-like like 2 (NELL2) and engaged in sperm maturation in the epididymis. At present, the recombinant expression of NICOL is not efficient, which limits the precise understanding of the structure and function of NICOL. In this study, we first succeeded in the chemical synthesis of NICOL with NELL2 binding affinity. The synthesized NICOL possesses correct SS bond pairing, and its secondary structure is indistinguishable from that of the recombinant protein, indicating that the synthetic NICOL will be useful for structural and functional analyses of lumicrine signaling.