| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2016: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
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| Outline of Final Research Achievements |
Through the synthetic studies of (Z)-chloroalkene-type ADIs (alkene dipeptide isosteres) for developing non-hydrolyzable peptidomimetics of human neuromedin U receptor 2 peptidic agonists, we have shown that the combination of SET reduction and asymmetric alkylation offers promising access to the precursors of the Arg-Asn-type ADIs. Also, the stereoselective synthesis of (Z)-chloroalkene-type ADIs containing alpha,alpha-disubstituted amino acids was established. Functional analyses revealed the unique characters of (Z)-chloroalkene-type ADIs, including the mimic effect of intraresidue H-bonding interactions. The amide-to-alkene isosteric switching strategy with the combination use of (Z)-chloroalkene-type and (E)-methylalkene-type peptidomimetics revealed the details of the contributions of H-bonding interactions in amyloid fibril formation.
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