Structure-Affinity Relationships of C-terminal Cyclic Analogue of Neuropeptide Y for the Y_1-Receptor

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概要

• 論文の詳細を見る

• We previously reported that a cyclic octapeptide amide, c[D-Cys^<29>, Cys^<34>]NPY Ac-29-36 (YM-42454) showed a high affinity for Y_1-receptors in SK-N-MC cells (K_i=0.047μM) but not for Y_2-receptors in the porcine hippocampus membranes (K_i>10μM). To explore the critical residues of this unique cyclic peptide for Y_1-binding activity, the structure-affinity relationships were investigated by means of amino acid replacement. The results indicated that the hydrophobic side-chains of Leu^<30> and Ile^<31>, the guanidinium groups of Arg^<33> and Arg^<35>, and the C-terminal amide are critical for the binding affinity of YM-42454 to the Y_1-receptor. On the other hand, Thr^<32> in YM-42454 might not be critical for the Y_1-binding affinity. ^1H-NMR studies for YM-42454 and its derivatives have suggested that the critical residues are involved in the direct interaction with a Y_1-receptor rather than in maintaining the bioactive conformation.

• 公益社団法人日本薬学会の論文
• 2000-12-01

著者

• Kakeya Hiroshi

  長崎大学 医学部第二内科

• Hara K

  Izumikawa Hospital

• Hara Kohei

  帝京大学 医学部

• Koga H

  The Second Department Of Internal Medicine Nagasaki University School Of Medicine

• Koga H

  Lead Discovery Laboratories Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Koga Hironobu

  長崎大学 第2内科

• Koga Hironobu

  The Second Department Of Internal Medicine Nagasaki University School Of Medicine

• Koga Hironobu

  山之内製薬

• Tanaka A

  Faculty Of Pharmaceutical Sciences Tokyo University Of Science

• Koga Hironobu

  Lead Discovery Laboratories Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• TAKEBAYASHI Yukihiro

  Lead Discovery Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., L

• TOGAMI Junji

  Applied Clinical Development Department, Yamanouchi Pharmaceutical Co., Ltd.,

• INUI Akio

  Lead Discovery Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., L

• KURIHARA Hiroyuki

  Lead Discovery Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., L

• FURUYA Toshio

  Lead Discovery Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., L

• TANAKA Akihiro

  Applied Clinical Development Department, Yamanouchi Pharmaceutical Co., Ltd

• MURASE Kiyoshi

  Bulk Manufacturing & Technology Division, Yamanouchi Pharmaceutical Co., Ltd.,

• Takebayashi Yukihiro

  Lead Discovery Laboratories Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Hara Kohei

  Second Department Of Internal Medicine Nagasaki University School Of Medicine

• Inui Akio

  Lead Discovery Laboratories Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Togami Junji

  Applied Clinical Development Department Yamanouchi Pharmaceutical Co. Ltd.

• Furuya Toshio

  Lead Discovery Laboratories Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Murase Kiyoshi

  Bulk Manufacturing & Technology Division Yamanouchi Pharmaceutical Co. Ltd.

• Hara Kohei

  長崎大学 第2内科

• Kurihara Hiroyuki

  Lead Discovery Laboratories Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Murase K

  Pharmacology Research Laboratories Ii Pharmaceutical Reseach Division Takeda Chemical Industries Ltd

• Tanaka Akihiro

  Applied Clinical Development Department Yamanouchi Pharmaceutical Co. Ltd

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