JP2016520585A - 修飾コラーゲン分子 - Google Patents
修飾コラーゲン分子 Download PDFInfo
- Publication number
- JP2016520585A JP2016520585A JP2016512879A JP2016512879A JP2016520585A JP 2016520585 A JP2016520585 A JP 2016520585A JP 2016512879 A JP2016512879 A JP 2016512879A JP 2016512879 A JP2016512879 A JP 2016512879A JP 2016520585 A JP2016520585 A JP 2016520585A
- Authority
- JP
- Japan
- Prior art keywords
- collagen
- collagen molecule
- molecule according
- peptide
- chondroitin sulfate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000001946 ultra-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
- 235000014393 valine Nutrition 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
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Abstract
Description
本出願は、2013年5月9日出願のシンガポール出願第201303597−7号の優先権の恩典を主張するものであり、前記シンガポール出願の内容は、あらゆる目的でその全体が参照により本明細書に援用されている。
本発明は、生体材料およびそれらの合成、特にコラーゲン分子の分野に存する。
少なくとも1本の鎖が一般式:
(X1−X2−G)n
(式中、
X1またはX2は、いずれのアミノ酸またはアミノ酸誘導体であってもよいが、但し、X1またはX2の少なくとも一方がグリコサミノグリカン部分であることを条件とし;
Gは、グリシンであり;および
nは、正の整数であり、かつ少なくとも1である)
の少なくとも1つの繰り返し単位を含む、前記コラーゲン分子を提供する。
少なくとも1本の鎖が一般式:
(X1−X2−G)n
(式中、
X1またはX2は、いずれのアミノ酸またはアミノ酸誘導体であってもよいが、但し、X1またはX2の少なくとも一方がグリコサミノグリカン部分であることを条件とし;
Gは、グリシンであり;および
nは、正の整数であり、かつ少なくとも1である)
の少なくとも1つの繰り返し単位を含む、前記コラーゲン分子を提供する。
少なくとも1本の鎖が一般式:
(X1−X2−G)n
(式中、
X1またはX2は、いずれのアミノ酸またはアミノ酸誘導体であってもよいが、但し、X1またはX2の少なくとも一方がグリコサミノグリカン部分であることを条件とし;
Gは、グリシンであり;および
nは、正の整数であり、かつ少なくとも1である)
の少なくとも1つの繰り返し単位を含む、前記コラーゲン分子を提供する。
トリメチルシリルトリフラートを使用して、トリクロロアセトイミダート4
を完全保護二糖5
に変換する工程;
N−トリクロロアセチル(N−trichloroacytl)基をn−トリブチルスタンナンおよびAIBNでN−アセチル同族体(cogner)に還元して、アセトアミド6
を得る工程;
ベンジリデンアセタールを加水分解し、続いてTMS基を脱保護してジオール7
を生成する工程;
シアン化ベンゾイルを使用してC6ヒドロキシル基を選択的にベンゾイル化して作用物質8:
を得る工程;
作用物質8をSO3−トリメチルアミン錯体で処理する工程;および
得られた混合物をLiOOHおよびNaOHで処理する工程
によって合成することができる。
特定の実施例を参照することによって、本発明の非限定的な例および比較例をさらにより詳細に説明することにする。これらの特定の実施例を、いかなる点においても、本発明の範囲を限定するものと解釈してはならない。
表1.ホモおよびヘテロ三量体の融解温度
[a]フォールディングされている画分の導関数プロットの最小値を用いて融解温度(Tm)を示す;[b]ペプチドを1:2の比で混合した;[c]ペプチドを予熱して確実に平衡させた;[d]予熱した1−3のTmをDSCによって判定した。
表2.ペプチドの分析HPLC条件
*A:CH3CN/0.1%TFA、B:H2O/0.1%TFA
表3.ペプチドのESI−MSデータ
[θ]=θ/(10・N・c・l)
θは、ミリ度での楕円率を表し、Nは、アミノ酸残基数を表し、cは、mol・L−1でのモル濃度を表し、lは、cmでのセル路長を表す。0.2mMの最終ペプチド濃度で熱変性曲線を得、225nmでのモル楕円率を、10℃/時の加熱速度で5〜80℃の範囲の温度の関数として測定した。アニールされたすべての試料を30分間85℃で加熱し、続いて1℃/分の速度で4℃に冷却し、続いて24時間、4℃で平衡させた後、測定した。融解曲線の一次導関数の最小点から融解温度を決定した。
Claims (23)
- 3本の鎖を含むコラーゲン分子であって、
少なくとも1本の鎖が一般式:
(X1−X2−G)n
(式中、
X1またはX2は、いずれのアミノ酸またはアミノ酸誘導体であってもよいが、但し、X1またはX2の少なくとも一方がグリコサミノグリカン部分であることを条件とし;
Gは、グリシンであり;および
nは、正の整数であり、かつ少なくとも1である)
の少なくとも1つの繰り返し単位を含む、前記コラーゲン分子。 - nが少なくとも2、または少なくとも5、または少なくとも10、または少なくとも20、または少なくとも50、または少なくとも100、または少なくとも200、または少なくとも500、または少なくとも1000である、請求項1に記載のコラーゲン分子。
- 前記グリコサミノグリカン部分が、少なくとも1つの二糖単位から成る、請求項1または2に記載のコラーゲン分子。
- 前記グリコサミノグリカン部分が、少なくとも1つの負荷電基を含有する、請求項3に記載のコラーゲン分子。
- 前記負荷電基が、スルファートまたはカルボキシラートである、請求項4に記載のコラーゲン分子。
- 前記グリコサミノグリカンが、コンドロイチン硫酸、ヘパリン、ヘパリン硫酸、デルマタン硫酸、ヒアルロナン、ケラタン硫酸および非硫酸化コンドロイチンから成る群より選択される、請求項1から5のいずれか一項に記載のコラーゲン分子。
- 前記コンドロイチン硫酸が、コンドロイチン硫酸A、コンドロイチン硫酸C、コンドロイチン硫酸D、コンドロイチン硫酸E、コンドロイチン硫酸U、コンドロイチン硫酸Kおよびコンドロイチン硫酸Lから成る群より選択される、請求項6に記載のコラーゲン分子。
- 前記コンドロイチン硫酸が、コンドロイチン硫酸Aまたはコンドロイチン硫酸Uである、請求項7に記載のコラーゲン分子。
- 前記アミノ酸が、正荷電アミノ酸である、請求項1から8のいずれか一項に記載のコラーゲン分子。
- 前記正荷電アミノ酸が、Asp、Glu、Lys、ArgおよびHisから成る群より選択される、請求項9に記載のコラーゲン分子。
- 前記コラーゲン鎖の少なくとも1本が、
Ac−(PXG)3−(CS−U−XG)2−(PXG)3−C(O)NH2、
Ac−(PXG)3−(CS−A−XG)2−(PXG)3−C(O)NH2、
Ac−(PXG)2−(CS−A−XG)4−(POG)2−C(O)NH2
(これらの式中、
Acは、アセチルであり;
Pは、プロリンであり;
Gは、グリシンであり;
CS−Uは、非硫酸化コンドロイチン硫酸であり;
CS−Aは、コンドロイチン硫酸Aであり;
Kは、リシンであり;
Rは、アルギニンであり;および
Xは、ヒドロキシプロリンである)
から成る群より選択される一般式を有する、請求項1から10のいずれか一項に記載のコラーゲン分子。 - 治療に使用するための、請求項1〜13のいずれか一項に記載のコラーゲン分子。
- 請求項1から13のいずれか一項に記載のコラーゲン分子を投与することを含む、治療を必要とする患者を処置する方法。
- 化粧品に使用するための、請求項1から13のいずれか一項に記載のコラーゲン分子。
- 組織工学に使用するための、請求項1から13のいずれか一項に記載のコラーゲン分子。
- 前記組織工学が、皮膚組織工学である、請求項17に記載のコラーゲン分子。
- 足場の構築に使用するための、請求項1から13のいずれか一項に記載のコラーゲン分子。
- 請求項1から13のいずれか一項に記載のコラーゲン分子と1つ以上の賦形剤とを含む組成物。
- グリコサミノグリカンに基づく薬学に使用するための、請求項1から13のいずれか一項に記載のコラーゲン分子。
- 組織工学用の生体材料として使用するための、請求項1から13のいずれか一項に記載のコラーゲン分子。
- 薬物送達または創傷治癒に使用するための、請求項1から13のいずれか一項に記載のコラーゲン分子。
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WO2013023137A2 (en) * | 2011-08-10 | 2013-02-14 | William Marsh Rice University | Multi-hierarchical self-assembly of a collagen mimetic peptide |
JP6051619B2 (ja) * | 2012-06-29 | 2016-12-27 | Jnc株式会社 | コラーゲン様ポリペプチドの製造方法 |
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- 2014-05-09 CN CN201480037498.7A patent/CN105392799A/zh active Pending
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- 2014-05-09 SG SG11201509238WA patent/SG11201509238WA/en unknown
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