JP2011510977A - ヘリコバクター・ピロリ菌のリボソームタンパク質l1由来の新しい抗生ペプチド及びその使用 - Google Patents
ヘリコバクター・ピロリ菌のリボソームタンパク質l1由来の新しい抗生ペプチド及びその使用 Download PDFInfo
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Abstract
【選択図】図1
Description
本発明者等は、メリフィールドの液状固相法(Merrifield,RB.,J.Am.Chem.Soc.,1963年,第85巻,p.2149)にしたがって、母体ペプチドである配列番号1で表わされるアミノ酸配列を有するHPA3NT3(比較群)から疎水性部分である1番と8番位置に二つのフェニルアラニンをフェニル基がないアラニンに転換して、NT3−F1AF8Aペプチド(配列番号2)(実験群1)を合成し、前記NT3−F1AF8Aペプチドから陽イオン電荷を増加させるために13番位置の負電荷アミノ酸であるアスパラギンを正電荷アミノ酸であるリジンに転換してNT3−F1AF8A−A2ペプチド(配列番号3)(実験群2)を合成した(表1)。
本発明者等は、前記<実施例1>の方法で製造されたペプチドの抗菌活性を比較するために、菌体が分裂しないペプチドの最小濃度である生育最小阻害濃度(MIC)値を測定した。
本発明者等は、前記<実施例1>の方法で製造されたペプチドの細胞毒性を比較するために、ペプチドの赤血球溶血活性を測定した。
式中、吸光度Aは414nm波長でのペプチド溶液の吸光度、吸光度Bは414nm波長でのPBSの吸光度、そして吸光度Cは414nm波長での1%トリトンX−100の吸光度を示す。
本発明者等は、前記<実施例1>の方法で製造されたペプチドの正常細胞株での細胞毒性を確認するため、ヒトの角質形成細胞株(HaCaT cell line,Dr.NE.Fusenig,Heidelberg,Germany)及びマウス線維芽細胞株(NIH3T3 cell line,ATCC(CRL−1658TM))を用いて毒性を測定した。
抗生ペプチド5.0mgを篩にかけた後、ラクトース14.1mg、クロスポビドン USNF0.8mg及びステアリン酸マグネシウム0.1mgを混合して加圧して錠剤に製造した。
抗生ペプチド5.0mgを篩にかけた後、ラクトース16.0mgと澱粉4.0mgを混ぜた。ポリソルベート80 0.3mgを純粋な水に溶解した後、この溶液の適量を添加した後、微粒化した。乾燥後に微粒を篩にかけた後、コロイダルシリコンジオキサイド2.7mg及びステアリン酸マグネシウム2.0mgと混合しぜた。微粒を加圧して錠剤に製造した。
抗生ペプチド5.0mgを篩にかけた後、ラクトース14.8mg、ポリビニルピロリドン10.0mg、ステアリン酸マグネシウム0.2mgとともに混合した。前記混合物を適当な装置を用いて堅いNo.5ゼラチンカプセルに充填した。
抗生ペプチド100mgを含有させ、その外にもマンニトール180mg、Na2HPO412H2O 26mg及び蒸留水2974mgを含有して注射剤を製造した。
配列番号2:NT3−F1AF8Aペプチド
配列番号3:NT3−F1AF8A−A2ペプチド
Claims (15)
- 配列番号1で表わされるアミノ酸配列を有する抗生ペプチドの1番及び8番位置のフェニルアラニン(Phenylalanine、F)がアラニン(alanine、A)に置換された細胞毒性が減少された抗生ペプチド。
- 前記抗生ペプチドが、配列番号2で表わされることを特徴とする、請求項1記載の抗生ペプチド。
- 配列番号2で表わされるアミノ酸配列を有する抗生ペプチドの13番位置のアスパラギン(Asparagine、N)が、正電荷アミノ酸に置換された抗生ペプチド。
- 前記抗生ペプチドが、配列番号3で表わされるアミノ酸配列を有することを特徴とする、請求項3記載の抗生ペプチド。
- 前記正電荷アミノ酸が、リジン(lysine,K)、アルギニン(arginine,R)及びヒスチジン(histidine,H)からなる群から選択されたいずれかひとつであることを特徴とする、請求項3記載の抗生ペプチド。
- 前記正電荷アミノ酸が、リジンであることを特徴とする、請求項5記載の抗生ペプチド。
- 請求項1または請求項3の抗生ペプチドを有効成分として含む抗生剤。
- 前記抗生剤が、グラム陰性菌またはグラム陽性菌に大海抗菌活性を有することを特徴とする、請求項7記載の抗生剤。
- 前記グラム陰性菌が、大腸菌(Escherichia coli)、緑膿菌(Pseudomonas aeruginosa)、P.ブルガリス(Proteus vulgaris)及びネズミチフス菌(Salmonella typhimurium)からなる群から選択されたいずれか一つであることを特徴とする、請求項8記載の抗生剤。
- 前記グラム陽性菌が、S.アウレウス(Staphylococcus aureus)、L.モノサイトゲネス(Listeria monocytogenes)、S.エピデルミデイス(Staphylococcus epidermidis)及びB.サブチリス(Bacillus subtilis)からなる群から選択されたいずれか一つであることを特徴とする、請求項8記載の抗生剤。
- 薬学的に有効な量の請求項7の抗生剤を病原性細菌疾患にかかった個体に投与する工程を含む病原性細菌疾患治療方法。
- 薬学的に有効な量の請求項7の抗生剤を個体に投与する工程を含む病原性細菌疾患予防方法。
- 請求項1または請求項3の抗生ペプチドの抗生剤の製造における使用。
- 請求項1または請求項3の抗生ペプチドを有効成分として含む食品補助剤または食品添加剤。
- 請求項1または請求項3の抗生ペプチドの食品補助剤または食品添加剤の製造における使用。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/KR2008/006938 WO2010061984A1 (en) | 2008-11-25 | 2008-11-25 | Novel antibiotic peptide derived from ribosomal protein l 1 of helicobacter pylori and use thereof |
Publications (2)
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JP2011510977A true JP2011510977A (ja) | 2011-04-07 |
JP5202649B2 JP5202649B2 (ja) | 2013-06-05 |
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JP2010544878A Expired - Fee Related JP5202649B2 (ja) | 2008-11-25 | 2008-11-25 | ヘリコバクター・ピロリ菌のリボソームタンパク質l1由来の新しい抗生ペプチド及びその使用 |
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Country | Link |
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US (1) | US8410046B2 (ja) |
JP (1) | JP5202649B2 (ja) |
CA (1) | CA2711462C (ja) |
WO (1) | WO2010061984A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102219831B (zh) * | 2011-04-18 | 2013-03-20 | 江苏普莱医药生物技术有限公司 | 一种抗菌肽及其制备方法和应用 |
US9278121B2 (en) * | 2013-03-14 | 2016-03-08 | The Board Of Trustees Of The University Of Arkansas | Methods of use for an antimicrobial peptide |
KR101627455B1 (ko) * | 2015-03-10 | 2016-06-07 | 순천대학교 산학협력단 | 항균활성을 가지는 키메라 펩타이드 및 이를 함유하는 항균용 조성물 |
US11174288B2 (en) | 2016-12-06 | 2021-11-16 | Northeastern University | Heparin-binding cationic peptide self-assembling peptide amphiphiles useful against drug-resistant bacteria |
WO2021191903A1 (en) * | 2020-03-26 | 2021-09-30 | Bone Sci. Bio Ltd. | Pharmaceutical compositions comprising amphiphilic peptides and methods of use thereof |
Citations (3)
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KR20020049443A (ko) * | 2000-12-19 | 2002-06-26 | 함경수 | 헬리코박터 파이로리균의 리보좀 단백질 l1 유래의새로운 항생 펩타이드 및 그의 용도 |
KR20090022608A (ko) * | 2007-08-31 | 2009-03-04 | 조선대학교산학협력단 | 헬리코박터 파일로리균의 리보좀 단백질 l1유래의 유사체펩타이드로부터 풀림구조를 절단한 양이온 증가 항생펩타이드 및 항균 및 항진균용 조성물 |
KR20100058794A (ko) * | 2008-11-25 | 2010-06-04 | 조선대학교산학협력단 | 헬리코박터 파이로리균의 리보좀 단백질 l1 유래의 새로운 항생 펩타이드 및 그의 용도 |
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JP4969517B2 (ja) * | 2008-05-29 | 2012-07-04 | 愛三工業株式会社 | 燃料供給装置 |
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2008
- 2008-11-25 JP JP2010544878A patent/JP5202649B2/ja not_active Expired - Fee Related
- 2008-11-25 US US12/863,406 patent/US8410046B2/en not_active Expired - Fee Related
- 2008-11-25 WO PCT/KR2008/006938 patent/WO2010061984A1/en active Application Filing
- 2008-11-25 CA CA2711462A patent/CA2711462C/en not_active Expired - Fee Related
Patent Citations (3)
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KR20020049443A (ko) * | 2000-12-19 | 2002-06-26 | 함경수 | 헬리코박터 파이로리균의 리보좀 단백질 l1 유래의새로운 항생 펩타이드 및 그의 용도 |
KR20090022608A (ko) * | 2007-08-31 | 2009-03-04 | 조선대학교산학협력단 | 헬리코박터 파일로리균의 리보좀 단백질 l1유래의 유사체펩타이드로부터 풀림구조를 절단한 양이온 증가 항생펩타이드 및 항균 및 항진균용 조성물 |
KR20100058794A (ko) * | 2008-11-25 | 2010-06-04 | 조선대학교산학협력단 | 헬리코박터 파이로리균의 리보좀 단백질 l1 유래의 새로운 항생 펩타이드 및 그의 용도 |
Non-Patent Citations (3)
Title |
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JPN6012056527; Biochim.Biophys.Acta,Vol.1778(Jan.2008)p.229-241 * |
JPN6012056531; Biopolymers(Pept.Sci.),Vol.55(2000)p.4-30 * |
JPN6012056534; Biochim.Biophys.Acta,Vol.1758(2006)p.1436-1449 * |
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Publication number | Publication date |
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JP5202649B2 (ja) | 2013-06-05 |
US20110053834A1 (en) | 2011-03-03 |
WO2010061984A1 (en) | 2010-06-03 |
CA2711462C (en) | 2016-05-24 |
US8410046B2 (en) | 2013-04-02 |
CA2711462A1 (en) | 2010-06-03 |
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