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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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:
Figure 2004529067
(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:
Figure 2004529067
(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。
JP2002533901A 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 Expired - Fee Related JP5196700B2 (ja)

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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

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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

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JP2004529067A JP2004529067A (ja) 2004-09-24
JP2004529067A5 true JP2004529067A5 (ja) 2009-07-02
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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
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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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