Based on our "Peptide to Non-peptide Chemistry" strategy, we are now focusing our efforts to develop peptide-lead conformationally restricted templates for genome-lead drug discovery.

            Recent investigations of this strategy focus on its application for downsizing and non-peptidylation of a 14-peptide CXCR4 antagonist, the receptor of which is relevant to several problematic diseases (cancer metastasis, AIDS, rheumatoid arthritis, etc.), as a practice in combination with CART (Constitutively Active Receptor Technology). Of note, the biostable CXCR4 antagonist, as a chemical probe, served to disclose the many physiological and pathological functions of CXCR4 including its important role for the formation of the dark zone and light zone appeared in germinal center of lymph node (70 years mystery). A new method for the facile synthesis of membrane embedded peptides utilizing lipid bilayer-asisted chemical ligation has been also developed aiming at the chemical synthesis of CXCR4, which is classified to 7TM-GPCR family.