JP2004529067A5 - - Google Patents
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- JP2004529067A5 JP2004529067A5 JP2002533901A JP2002533901A JP2004529067A5 JP 2004529067 A5 JP2004529067 A5 JP 2004529067A5 JP 2002533901 A JP2002533901 A JP 2002533901A JP 2002533901 A JP2002533901 A JP 2002533901A JP 2004529067 A5 JP2004529067 A5 JP 2004529067A5
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- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 31
- 125000000267 glycino group Chemical group [H]N([*])C([H])([H])C(=O)O[H] 0.000 description 30
- 125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 description 29
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 27
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 26
- MTCFGRXMJLQNBG-REOHCLBHSA-N L-serine Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 25
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 25
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 19
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 18
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 16
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 16
- 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 0.000 description 14
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 13
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 13
- XUJNEKJLAYXESH-REOHCLBHSA-N L-cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 12
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 9
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 6
- -1 His Chemical compound 0.000 description 5
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 5
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 241000252212 Danio rerio Species 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 229920000665 Exon Polymers 0.000 description 1
- 240000001340 Gmelina philippensis Species 0.000 description 1
- 230000000875 corresponding Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
Description
例示的具体例において、Shhクローンの各々のエキソン1、2及びエキソン3の一部にコードされる配列(例えば、成熟タンパク質のN末端の約221残基)のアラインメントは、下記の一般式により表されるShhポリペプチドの縮重セットを生成する:
(式中、縮重位置「X」の各々は、ヒト、マウス、ニワトリ又はゼブラフィッシュのShhクローンの一つにおいてその位置に出現するアミノ酸であってよく、又は、このライブラリーを拡大するために、各Xを、それらの位置に天然において出現するアミノ酸についての保存的置換であるアミノ酸残基中から選択することもできる)。例えば、Xaa(1)は、Gly、Ala、Val、Leu、Ile、Phe、Tyr又はTrpを表し;Xaa(2)は、Arg、His又はLysを表し;Xaa(3)は、Gly、Ala、Val、Leu、Ile、Ser又はThrを表し;Xaa(4)は、Gly、Ala、Val、Leu、Ile、Ser又はThrを表し;Xaa(5)は、Lys、Arg、His、Asn又はGlnを表し;Xaa(6)は、Lys、Arg又はHisを表し;Xaa(7)は、Ser、Thr、Tyr、Trp又はPheを表し;Xaa(8)は、Lys、Arg又はHisを表し;Xaa(9)は、Met、Cys、Ser又はThrを表し;Xaa(10)は、Gly、Ala、Val、Leu、Ile、Ser又はThrを表し;Xaa(11)は、Leu、Val、Met、Thr又はSerを表し;Xaa(12)は、His、Phe、Tyr、Ser、Thr、Met又はCysを表し;Xaa(13)は、Gln、Asn、Glu又はAspを表し;Xaa(14)は、His、Phe、Tyr、Thr、Gln、Asn、Glu又はAspを表し;Xaa(15)は、Gln、Asn、Glu、Asp、Thr、Ser、Met又はCysを表し;Xaa(16)は、Ala、Gly、Cys、Leu、Val又はMetを表し;Xaa(17)は、Arg、Lys、Met、Ile、Asn、Asp、Glu、Gln、Ser、Thr又はCysを表し;Xaa(18)は、Arg、Lys、Met又はIleを表し;Xaa(19)は、Ala、Gly、Cys、Asp、Glu、Gln、Asn、Ser、Thr又はMetを表し;Xaa(20)は、Ala、Gly、Cys、Asp、Asn、Glu又はGlnを表し;Xaa(21)は、Arg、Lys、Met、Ile、Asn、Asp、Glu又はGlnを表し;Xaa(22)は、Leu、Val、Met又はIleを表し;Xaa(23)は、Phe、Tyr、Thr、His又はTrpを表し;Xaa(24)は、Ile、Val、Leu又はMetを表し;Xaa(25)は、Met、Cys、Ile、Leu、Val、Thr又はSerを表し;Xaa(26)は、Leu、Val、Met、Thr又はSerを表す。尚一層広範なライブラリーにおいては、各Xは、任意のアミノ酸から選択することができる。
類似の様式で、ヒト、マウス、ニワトリ及びゼブラフィッシュヘッジホッグクローンの各々のアラインメントは、下記の一般式により表される縮重ポリペプチド配列を与えることができる:
(式中、縮重位置「X」の各々は、上記のように、野生型クローンの一つにおける対応位置に出現するアミノ酸であってよく、保存的置換であるアミノ酸残基を含むこともでき、又は各Xは、任意のアミノ酸残基であってよい)。典型的具体例において、Xaa(1)は、Gly、Ala、Val、Leu、Ile、Pro、Phe又はTyrを表し;Xaa(2)は、Gly、Ala、Val、Leu又はIleを表し;Xaa(3)は、Gly、Ala、Val、Leu、Ile、Lys、His又はArgを表し;Xaa(4)は、Lys、Arg又はHisを表し;Xaa(5)は、Phe、Trp、Tyr又はアミノ酸ギャップを表し;Xaa(6)は、Gly、Ala、Val、Leu、Ile又はアミノ酸ギャップを表し;Xaa(7)は、Asn、Gln、His、Arg又はLysを表し;Xaa(8)は、Gly、Ala、Val、Leu、Ile、Ser又はThrを表し;Xaa(9)は、Gly、Ala、Val、Leu、Ile、Ser又はThrを表し;Xaa(10)は、Gly、Ala、Val、Leu、Ile、Ser又はThrを表し;Xaa(11)は、Ser、Thr、Gln又はAsnを表し;Xaa(12)は、Met、Cys、Gly、Ala、Val、Leu、Ile、Ser又はThrを表し;Xaa(13)は、Gly、Ala、Val、Leu、Ile又はProを表し;Xaa(14)は、Arg、His又はLysを表し;Xaa(15)は、Gly、Ala、Val、Leu、Ile、Pro、Arg、His又はLysを表し;Xaa(16)は、Gly、Ala、Val、Leu、Ile、Phe又はTyrを表し;Xaa(17)は、Arg、His又はLysを表し;Xaa(18)は、Gly、Ala、Val、Leu、Ile、Ser又はThrを表し;Xaa(19)は、Thr又はSerを表し;Xaa(20)は、Gly、Ala、Val、Leu、Ile、Asn又はGlnを表し;Xaa(21)は、Arg、His又はLysを表し;Xaa(22)は、Asp又はGluを表し;Xaa(23)は、Ser又はThrを表し;Xaa(24)は、Glu、Asp、Gln又はAsnを表し;Xaa(25)は、Glu又はAspを表し;Xaa(26)は、Arg、His又はLysを表し;Xaa(27)は、Gly、Ala、Val、Leu又はIleを表し;Xaa(28)は、Gly、Ala、Val、Leu、Ile、Thr又はSerを表し;Xaa(29)は、Met、Cys、Gln、Asn、Arg、Lys又はHisを表し;Xaa(30)は、Arg、His又はLysを表し;Xaa(31)は、Trp、Phe、Tyr、Arg、His又はLysを表し;Xaa(32)は、Gly、Ala、Val、Leu、Ile、Ser、Thr、Tyr又はPheを表し;Xaa(33)は、Gln、Asn、Asp又はGluを表し;Xaa(34)は、Asp又はGluを表し;Xaa(35)は、Gly、Ala、Val、Leu又はIleを表し;Xaa(36)は、Arg、His又はLysを表し;Xaa(37)は、Asn、Gln、Thr又はSerを表し;Xaa(38)は、Gly、Ala、Val、Leu、Ile、Ser、Thr、Met又はCysを表し;Xaa(39)は、Gly、Ala、Val、Leu、Ile、Thr又はSerを表し;Xaa(40)は、Arg、His又はLysを表し;Xaa(41)は、Asn、Gln、Gly、Ala、Val、Leu又はIleを表し;Xaa(42)は、Gly、Ala、Val、Leu又はIleを表し;Xaa(43)は、Gly、Ala、Val、Leu、Ile、Ser、Thr又はCysを表し;Xaa(44)は、Gly、Ala、Val、Leu、Ile、Thr又はSerを表し;そしてXaa(45)は、Asp又はGluを表す。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US24056400P | 2000-10-13 | 2000-10-13 | |
US60/240,564 | 2000-10-13 | ||
PCT/US2001/032100 WO2002030462A2 (en) | 2000-10-13 | 2001-10-15 | Hedgehog antagonists, methods and uses related thereto |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008101692A Division JP2008214356A (ja) | 2000-10-13 | 2008-04-09 | ヘッジホッグアンタゴニスト、それらに関する方法及び利用 |
JP2009113082A Division JP2009179630A (ja) | 2000-10-13 | 2009-05-07 | ヘッジホッグアンタゴニスト、それらに関する方法及び利用 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2004529067A JP2004529067A (ja) | 2004-09-24 |
JP2004529067A5 true JP2004529067A5 (ja) | 2009-07-02 |
JP5196700B2 JP5196700B2 (ja) | 2013-05-15 |
Family
ID=22907059
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2002533901A Expired - Fee Related JP5196700B2 (ja) | 2000-10-13 | 2001-10-15 | ヘッジホッグアンタゴニスト、それらに関する方法及び利用 |
JP2008101692A Abandoned JP2008214356A (ja) | 2000-10-13 | 2008-04-09 | ヘッジホッグアンタゴニスト、それらに関する方法及び利用 |
JP2009113082A Pending JP2009179630A (ja) | 2000-10-13 | 2009-05-07 | ヘッジホッグアンタゴニスト、それらに関する方法及び利用 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008101692A Abandoned JP2008214356A (ja) | 2000-10-13 | 2008-04-09 | ヘッジホッグアンタゴニスト、それらに関する方法及び利用 |
JP2009113082A Pending JP2009179630A (ja) | 2000-10-13 | 2009-05-07 | ヘッジホッグアンタゴニスト、それらに関する方法及び利用 |
Country Status (8)
Country | Link |
---|---|
US (2) | US20040060568A1 (ja) |
EP (1) | EP1387674B1 (ja) |
JP (3) | JP5196700B2 (ja) |
AU (3) | AU2001296844B2 (ja) |
CA (1) | CA2425356C (ja) |
DK (1) | DK1387674T3 (ja) |
ES (1) | ES2623711T3 (ja) |
WO (1) | WO2002030462A2 (ja) |
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JP3776454B2 (ja) * | 1994-10-07 | 2006-05-17 | ザ ボード オブ トラスティーズ オブ ザ リーランド スタンフォード ジュニア ユニバーシティ | パッチド遺伝子及びそれらの使用 |
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DE60028411T2 (de) * | 1999-10-13 | 2007-01-04 | Johns Hopkins University School Of Medicine | Verbindungen zur regulierung des hedgehog-signalwegs, zusammensetzungen und verwendungen davon |
ATE324876T1 (de) | 1999-10-14 | 2006-06-15 | Curis Inc | VERMITTLER VON ßHEDGEHOGß ÜBERMITTELNDEN BAHNEN, DAZUGEHÖRIGE ZUSAMMENETZUNGEN UND VERWENDUNGEN |
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-
2001
- 2001-10-15 US US09/977,864 patent/US20040060568A1/en not_active Abandoned
- 2001-10-15 AU AU2001296844A patent/AU2001296844B2/en not_active Ceased
- 2001-10-15 DK DK01977751.5T patent/DK1387674T3/en active
- 2001-10-15 ES ES01977751.5T patent/ES2623711T3/es not_active Expired - Lifetime
- 2001-10-15 WO PCT/US2001/032100 patent/WO2002030462A2/en active Application Filing
- 2001-10-15 CA CA2425356A patent/CA2425356C/en not_active Expired - Lifetime
- 2001-10-15 EP EP01977751.5A patent/EP1387674B1/en not_active Expired - Lifetime
- 2001-10-15 JP JP2002533901A patent/JP5196700B2/ja not_active Expired - Fee Related
- 2001-10-15 AU AU9684401A patent/AU9684401A/xx active Pending
-
2006
- 2006-10-20 AU AU2006230725A patent/AU2006230725B2/en not_active Ceased
-
2008
- 2008-04-09 JP JP2008101692A patent/JP2008214356A/ja not_active Abandoned
-
2009
- 2009-05-07 JP JP2009113082A patent/JP2009179630A/ja active Pending
-
2010
- 2010-06-01 US US12/791,785 patent/US8486400B2/en not_active Expired - Fee Related
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