Medicinal Chemistry of Mid-sized Molecules on Biologically Active Peptides
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- Hayashi Yoshio
- Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences
Bibliographic Information
- Other Title
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- ペプチド化学を利用した生体分子からの中分子創薬
- ペプチド カガク オ リヨウ シタ セイタイ ブンシ カラ ノ チュウ ブンシソウヤク
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Description
Neuromedin U (NMU) displays various physiological activities including an anorexigenic effect, and the C-terminal heptapeptide-amide sequence is necessary to activate two NMU receptors (NMUR1 and NMUR2). Based on this heptapeptide, we recently developed highly active NMUR1 hexapeptide agonist 4d and NMUR2-selective hexapeptide agonist 8c. Moreover, we identified two major biodegradation sites (Phe2-Arg3 and Arg5-Asn6) by the stability analysis of 4d in serum. On the other hand, myostatin is an endogenous negative regulator of skeletal muscle mass, which is recognized as a therapeutic target for muscle atrophic disorders. Recently, we successfully identified myostatin inhibitory peptides 9 and 16 (24 and 23 amino acids, respectively) with minimum sequence derived from mouse myostatin prodomain. These peptides directly bind to myostatin with KD values of 30-36 nM. Moreover, peptide 9 significantly increased tibialis anterior muscle mass in Duchenne muscular dystrophy model mice. Therefore, these synthesized peptides would be promising mid-sized molecules for peptide-based medicinal chemistry.
Journal
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- Journal of Synthetic Organic Chemistry, Japan
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Journal of Synthetic Organic Chemistry, Japan 73 (7), 737-748, 2015
The Society of Synthetic Organic Chemistry, Japan
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Keywords
Details 詳細情報について
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- CRID
- 1390282680318245504
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- NII Article ID
- 130005093746
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- NII Book ID
- AN0024521X
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- ISSN
- 18836526
- 00379980
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- NDL BIB ID
- 026607969
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed