2007 Fiscal Year Final Research Report Summary
Synthesis of retro-inverso peptides for a medicinal product that shows selectiveACE inhbtion
| Project/Area Number |
17590096
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Teikyo University |
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Principal Investigator |
NAKAGOMI Kazuya Teikyo University, School of Pharmaceutical Sciences, Professor (70272929)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Retro-inverso peptides / Angiotensin-l-converting enzyme inhibition / Anti-hypertension / Enzymatic hydrolysates of proteins / Val-Ala-Trp / Val-Ser-Trp / Tryotophan |
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| Research Abstract |
This research project focuses on the synthesis of novel retro-inverso peptide analogues, which have selective angiotensin-l-converting enzyme (ACE) inhibition. ACE raises blood pressure by converting angiotensin I (Ang I), decapeptide, into the potent vasoconstrictor angiotensin II (Ang II), octapeptide. ACE also egradates sodilative bradykinin (BK) in blood vessels. ACE inhbitors such as captopril inhbit both the conversion of Mg I and the degradation of BK that may cause several side effects in human body. We have noticed the selective ACE inhbition by peptides, which inhibit Ang I conversion but show no effect on BK degradation. The goal of this project is to offer an anti-hypertensive retro-inverso peptidyl product for medicinal use with no side effect by BK.
Some peptides Val Ala-Trp, Val-Ser-Trp and Ala-Trp, which have isolated irom enzymatic hydrolysates of human proteins, show selective ACE inhbition with little effect on BK degradation. The Ki ratio of these peptides were measu
… More
red 28, 22 and 64, respectively. On the other hand, that of ACE inhbitory peptides was measured below 10. Both C-terminal Tip residue and C-terminal carboxyl moiety needed to show selective inhibitory activity in comparison with other ACE inhibitory peptides.
Retro-inverso peptides consist of all D-amino adds with reversed direction. The side chains of these structures are thought same stereo-chemical position as those of normal peptides with L-amino adds. In addition, the retro-inverso peptides are thought resistant to the attack of proteolytic enzymes in human body.
We have synthesized a building unit m_dTrp-OtBu, t-butyl 2 (indol-3-y1)methyl malonate, to change amino moiety of Tip residue to carboxyl moiety. Using this unit we have synthesed m_d Trp-_dAla-_dVal-NH_2, retro-inverso peptidyl analogue with carboxyl moiety at the N-terminus. Although the inhibitional activity of this peptide analogue was not so potent, it was found to clearly inh bit Mg I conversion but not to inhibit BK degradation. Less
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Research Products
(97 results)
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[Journal Article] Analysis of alternation of L-Asp and L-Asn residues in peptides related to neuronal disease. 20062006
Author(s)
Sadakane, Y., Kuramoto, S., Konoha, K., Kawahara, M., Nakagomi, K
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Journal Title
Peptide Science, 2006 284
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Isolation of novel cathepsin B inhibitory peptides from enzymatic hydrolysates of human proteins2006
Author(s)
Koyama, H., Yasuda, M., Mawatari, K., Kaneko, K., Sadakane, Y., Hatanaka, Y., Nakagomi, K
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Journal Title
Peptide Science, 2006
Pages: 313-314
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Vasodilative effect of perillaldehyde on isolated rat aorta2005
Author(s)
Takagi, S., Goto, H., Shimada, Y., Nakagomi, K., Sadakane, Y., Hatanaka, Y
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Journal Title
Phytomedicine 12
Pages: 333-337
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Chiral ligand exchange micellar electrokinetic chromatography using borateanion as a central ion2005
Author(s)
Kodama, S., Yamamoto, A., Iio, R., Aizawa, S., Nakagomi, K., Hayakawa, K
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Journal Title
Electrophoresis 26 (20)
Pages: 3884-9
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Analysis of urinary calculi obtained from a patient with idiopathic hypouricemia using micro area x-ray diffractometry and LC-MS2005
Author(s)
Kaneko, K., Yamanobe, T., Onoda, M., Mawatari, K., Nakagomi, K., Fujimori, S
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Journal Title
Urol Res 33 (6)
Pages: 415-21
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 尿路結石の成分分析2008
Author(s)
泉 陽子, 中込 和哉, 他
Organizer
第41回日本痛風, 核酸代謝学会総会
Place of Presentation
福井
Year and Date
20080214-15
Description
「研究成果報告書概要(和文)」より
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[Presentation] Isolation of novel cathepsin B inhibitory peptides from enzymatic hydrolysates of human proteins2006
Author(s)
Koyama, H., Yasuda, M., Mawatari, K., Kaneko, K., Sadakane, Y., Hatanaka, Y., Nakagomi, K
Organizer
43rd Japanese Peptide Symposium/4th Peptide Engineering Meeting(43JPS/PEM4)
Place of Presentation
Yokohama
Year and Date
20061105-08
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Tryptophan containing angiotensin-I-converting enzyme inhibitory peptides from the enzymatic hydrolysate of human proteins2006
Author(s)
Nakagomi, K., Wakamiya, T., Koyama, H., Yasuda, M., Mawatari, K., Kaneko, K., Sadakane, Y., Hatanaka, Y
Organizer
The 11th Meeting of The International Study Group of Tryptophan Research-2006(ISTRY2006)
Place of Presentation
Tokyo
Year and Date
20060703-07
Description
「研究成果報告書概要(欧文)」より
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