JP2000290297A - 26 position-derivative of calcitonin - Google Patents
26 position-derivative of calcitoninInfo
- Publication number
- JP2000290297A JP2000290297A JP11092523A JP9252399A JP2000290297A JP 2000290297 A JP2000290297 A JP 2000290297A JP 11092523 A JP11092523 A JP 11092523A JP 9252399 A JP9252399 A JP 9252399A JP 2000290297 A JP2000290297 A JP 2000290297A
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- Prior art keywords
- calcitonin
- derivative
- aspartic acid
- residue
- acid residue
- Prior art date
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、新規なカルシトニ
ン誘導体に関するものである。詳しくは、２６位アスパ
ラギン酸残基をＮ−アセチル−Ｄ−グルコサミンが側鎖
アミド基の窒素原子に結合しているアスパラギン残基に
置換したカルシトニン、またはエルカトニン誘導体及び
２６位アスパラギン酸残基をアスパラギン残基に置換し
たカルシトニンまたはエルカトニン誘導体に関するもの
で、さらに詳しくは、２６位アスパラギン酸残基をＮ−
アセチル−Ｄ−グルコサミンが側鎖アミド基の窒素原子
に結合しているアスパラギン残基に置換したウナギ由来
カルシトニン誘導体、及び２６位アスパラギン酸残基を
アスパラギン残基に置換したウナギ由来カルシトニン誘
導体に関するものである。本発明は、医薬の分野に応用
される。[0001] The present invention relates to a novel calcitonin derivative. Specifically, calcitonin in which the aspartic acid residue at position 26 is substituted by an asparagine residue in which N-acetyl-D-glucosamine is bonded to the nitrogen atom of the side chain amide group, or an elcatonin derivative and the aspartic acid residue at position 26 are replaced with aspartic acid The present invention relates to a calcitonin or elcatonin derivative substituted with a residue.
The present invention relates to an eel-derived calcitonin derivative in which acetyl-D-glucosamine is substituted for an asparagine residue bonded to a nitrogen atom of a side chain amide group, and an eel-derived calcitonin derivative in which an aspartic acid residue at position 26 is substituted for an asparagine residue. is there. The present invention is applied to the field of medicine.
【０００２】[0002]
【従来の技術】カルシトニンは、３２残基のアミノ酸か
ら成るペプチドホルモンで、哺乳動物のカルシウム調節
ホルモンとして機能し、骨吸収を抑制することから、ヒ
ト、ブタ、サケ、ウナギのカルシトニンもしくはその誘
導体が骨粗鬆症等の治療薬として使用されている。2. Description of the Related Art Calcitonin is a peptide hormone consisting of 32 amino acids, which functions as a calcium-regulating hormone in mammals and suppresses bone resorption, so that calcitonin of human, pig, salmon and eel or a derivative thereof can be used. It is used as a therapeutic agent for osteoporosis and the like.
【０００３】カルシトニン類は、そのアミノ酸配列か
ら、主にヒトやブタに由来するタイプと、サケやウナギ
に由来するタイプに大別することが出来、骨吸収抑制能
に対応する血中カルシウム濃度低下作用等の活性では、
サケ等に由来するタイプのカルシトニン類の活性が高い
ことが知られている。蛋白質の一般的な修飾法として、
糖鎖を結合する手法が考えられる。糖蛋白質や糖脂質の
ような複合糖質の糖鎖は、細胞の基質認識、細胞間の認
識等に関わっており、また生体内物質の吸収分解や安定
性等に寄与している。[0003] Calcitonins can be roughly classified into those derived mainly from humans and pigs and those derived from salmon and eels based on their amino acid sequences, and have a decrease in blood calcium concentration corresponding to the ability to inhibit bone resorption. In activity such as action,
It is known that the activity of calcitonins derived from salmon and the like is high. As a general modification method of proteins,
A method of linking sugar chains is conceivable. The sugar chains of complex carbohydrates such as glycoproteins and glycolipids are involved in cell substrate recognition, intercellular recognition, etc., and also contribute to the absorption and decomposition and stability of biological substances.
【０００４】従って、元々糖鎖を持たないカルシトニン
についても、糖鎖を付加することにより、血中での安定
性、吸収代謝の改善や生理活性の向上が期待される。カ
ルシトニン類については、既に糖鎖を付加することによ
り、安定化や吸収代謝の改善あるいは投与経路の変更等
の効果が期待できるとして、稲津ら［特開平１０−１４
７５９６号（１９９８）］はウナギ由来カルシトニンの
１位から１０位までの部分ペプチドの３位アスパラギン
残基の側鎖アミド基の窒素原子にＮ−アセチルグルコサ
ミンがグリコシル化している誘導体、稲津ら［特開平１
０−１４７５９８号（１９９８）］は、ウナギ由来カル
シトニンの３位アスパラギン残基の側鎖アミド基の窒素
原子にＮ−アセチルグルコサミンがグリコシル化してい
る誘導体、また、羽田ら［特開平１０−１４７５９９号
（１９９８）］はウナギ由来カルシトニンの３位アスパ
ラギン残基の側鎖アミド基の窒素原子に複合型糖鎖、高
マンノース型糖鎖あるいは混成型糖鎖が結合している誘
導体について報告している。[0004] Therefore, even for calcitonin which originally has no sugar chain, by adding a sugar chain, stability in blood, improvement in absorption and metabolism and improvement in physiological activity are expected. With regard to calcitonins, stabilization, improvement in absorption and metabolism, and effects of changing the administration route can be expected by adding a sugar chain.
No. 7596 (1998)] discloses a derivative in which N-acetylglucosamine is glycosylated at the nitrogen atom of the side chain amide group of the asparagine residue at position 3 of the partial peptide from position 1 to position 10 of eel calcitonin. Kaiping 1
No. 0-147598 (1998)] is a derivative in which N-acetylglucosamine is glycosylated at the nitrogen atom of the side chain amide group of the 3-position asparagine residue of eel-derived calcitonin, and Haneda et al. [JP-A-10-147599]. (1998)] reports a derivative in which a complex type sugar chain, a high mannose type sugar chain, or a mixed type sugar chain is bonded to the nitrogen atom of the side chain amide group of the 3-position asparagine residue of eel calcitonin.
【０００５】しかしながら、依然として、糖鎖構造と結
合位置のペプチドの活性に与える影響に関しては、不明
な部分が多く、カルシトニンについても、どのような部
位に糖鎖を付加すれば、医薬としてより高い血中安定
性、薬理作用を持つようになるかについては明らかでは
ない。従って、糖鎖による修飾を用いて、カルシトニン
類の活性向上の為の一般的な手法が実現出来れば、カル
シトニン誘導体医薬品の開発の重要な手段と成り得る。However, the effects of the sugar chain structure and the binding position on the activity of the peptide are still largely unknown, and even if calcitonin is added to any part of the sugar chain, higher blood sugar as a medicine is obtained. It is not clear whether it will have moderate stability and pharmacological effects. Therefore, if a general method for improving the activity of calcitonin can be realized by using modification with a sugar chain, it can be an important means for developing a calcitonin derivative drug.
【０００６】[0006]
【発明が解決しようとする課題】本発明の目的は、血中
カルシウム濃度低下作用を有する新規なカルシトニン誘
導体を提供することである。SUMMARY OF THE INVENTION An object of the present invention is to provide a novel calcitonin derivative having a blood calcium concentration lowering action.
【０００７】[0007]
【課題を解決するための手段】本発明者らは、２６位の
アスパラギン酸残基がアスパラギン残基に置換されたウ
ナギ由来カルシトニン、及びその２６位のアスパラギン
残基の側鎖アミド基の窒素原子にＮ−アセチル−Ｄ−グ
ルコサミンを結合したウナギ由来カルシトニン誘導体の
合成を行い、それらの血中カルシウム濃度低下作用を測
定したところ、いずれの誘導体にも、ウナギ由来カルシ
トニンと同等以上の活性があることが判明し、本発明を
完成するに至った。Means for Solving the Problems The present inventors have found that eel calcitonin in which the aspartic acid residue at position 26 has been substituted with an asparagine residue, and the nitrogen atom of the side chain amide group of the asparagine residue at position 26 The synthesis of eel-derived calcitonin derivatives with N-acetyl-D-glucosamine bound to them, and their blood calcium concentration lowering effect was measured.Each derivative had an activity equal to or higher than that of eel-derived calcitonin. Has been found, and the present invention has been completed.
【０００８】すなわち、本発明は、（１）２６位アスパ
ラギン酸残基をアスパラギン残基に置換したカルシトニ
ンまたはエルカトニン誘導体、（２）２６位アスパラギ
ン酸残基をＮ−アセチル−Ｄ−グルコサミンが側鎖アミ
ド基の窒素原子に結合しているアスパラギン残基に置換
したカルシトニンまたはエルカトニン誘導体、（３）配
列表配列番号１で表される、２６位アスパラギン酸残基
をアスパラギン残基に置換したウナギ由来カルシトニン
誘導体、及び、（４）配列表配列番号２で表される、２
６位アスパラギン酸残基をＮ−アセチル−Ｄ−グルコサ
ミンが側鎖アミド基の窒素原子に結合しているアスパラ
ギン残基に置換したウナギ由来カルシトニン誘導体に関
する。That is, the present invention provides (1) a calcitonin or elcatonin derivative in which the aspartic acid residue at position 26 is substituted by an asparagine residue, and (2) a side chain of N-acetyl-D-glucosamine which substitutes for the aspartic acid residue at position 26. Calcitonin or elcatonin derivative substituted with an asparagine residue bonded to the nitrogen atom of an amide group, (3) eel calcitonin represented by SEQ ID NO: 1 in which an aspartic acid residue at position 26 is substituted with an asparagine residue Derivatives and (4) 2 represented by SEQ ID NO: 2
The present invention relates to an eel-derived calcitonin derivative in which the aspartic acid residue at position 6 is substituted with an asparagine residue in which N-acetyl-D-glucosamine is bonded to the nitrogen atom of the side chain amide group.
【０００９】以下、ウナギ由来カルシトニンの場合を例
として合成法を記載するが、２６位がアスパラギン酸残
基である多種由来のカルシトニンまたはエルカトニンの
場合においても、同様に合成される。２６位のアスパラ
ギン酸残基がアスパラギン残基に置換されたウナギ由来
カルシトニン誘導体の合成はいかなる方法によってもよ
いが、例えば、通常のペプチドと同様、固相法を用いて
合成が可能である。Hereinafter, the synthesis method will be described by taking the case of eel calcitonin as an example. In the case of calcitonin or elcatonin derived from various species in which the 26-position is an aspartic acid residue, the synthesis is similarly performed. The eel-derived calcitonin derivative in which the aspartic acid residue at position 26 has been substituted with an asparagine residue may be synthesized by any method. For example, it can be synthesized using a solid phase method, similarly to a general peptide.
【００１０】また、２６位アスパラギン酸残基をＮ−ア
セチル−Ｄ−グルコサミンが側鎖アミド基の窒素原子に
結合しているアスパラギン残基に置換したウナギ由来カ
ルシトニン誘導体の合成はいかなる方法によってもよい
が、例えば、３位のアスパラギン残基の側鎖アミド基の
窒素原子にＮ−アセチル−Ｄ−グルコサミンを結合した
ウナギ由来カルシトニンの合成に用いられた稲津らの方
法［特開平１０−１４７５９８号（１９９８）］に準じ
た方法を用いることも出来るし、豊島ら［ Teshima, T.
et al., 25-28, in "Peptide Chemistry 1996", Kitad
a, C. (ed.), Protein Research Fundation, Osaka (19
97) ］の開発した方法に従い、側鎖アミド基の窒素原子
にＮ−アセチル−Ｄ−グルコサミンを結合したアスパラ
ギンを適当に保護して、固相法Ｂｏｃストラテジーを用
いて合成することも可能である。その精製、分析に関し
ては、通常のペプチドの精製、分析に用いられる手法を
利用することが出来る。The synthesis of an eel-derived calcitonin derivative in which the aspartic acid residue at position 26 is substituted by an asparagine residue in which N-acetyl-D-glucosamine is bonded to the nitrogen atom of the side chain amide group may be performed by any method. Was used for the synthesis of eel-derived calcitonin in which N-acetyl-D-glucosamine was bonded to the nitrogen atom of the side chain amide group of the asparagine residue at the 3-position [In Japanese Patent Application Laid-Open No. Hei 10-147598 (JP-A-10-147598)]. 1998)], and Teshima et al. [Teshima, T. et al.
et al., 25-28, in "Peptide Chemistry 1996", Kitad
a, C. (ed.), Protein Research Fundation, Osaka (19
97)], the asparagine in which N-acetyl-D-glucosamine is bonded to the nitrogen atom of the side chain amide group can be appropriately protected, and the compound can be synthesized using the solid phase Boc strategy. . For the purification and analysis, a method used for ordinary peptide purification and analysis can be used.
【００１１】[0011]
【発明の実施の形態】以下に、本発明を更に具体的に説
明するが、本発明はこれに限定されるものではない。
尚、以下の実施例では、ウナギ由来カルシトニンをＣ
Ｔ、配列表配列番号１の誘導体をＮ２６−ＣＴ、配列表
配列番号２の誘導体をＧＮ２６−ＣＴと、略記する。BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described more specifically, but the present invention is not limited thereto.
In the following examples, eel-derived calcitonin was converted to C
T, the derivative of SEQ ID NO: 1 in the Sequence Listing is abbreviated as N26-CT, and the derivative of SEQ ID NO: 2 in the Sequence Listing is abbreviated as GN26-CT.
【００１２】[0012]
【実施例１】Ｎ２６−ＣＴの合成 Ｎ２６−ＣＴは、通常の固相法により合成を行った。Ｈ
ＰＬＣ［ＯＤＳ（ＹＭＣ Ｐａｋ ＯＤＳ−ＡＭ、φ
４．６×１５０ｍｍ）、展開溶媒０．１％トリフルオロ
酢酸／２０％〜７０％（２５分）アセトニトリル水溶
液、流速１．０ｍｌ／分］で２２０ｎｍの吸収により分
析すると、生成物のＮ２６−ＣＴは、保持時間１５．４
分のピークとして検出された。Example 1 Synthesis of N26-CT N26-CT was synthesized by a usual solid phase method. H
PLC [ODS (YMC Pak ODS-AM, φ
4.6 × 150 mm), developing solvent 0.1% trifluoroacetic acid / 20% to 70% (25 minutes) acetonitrile aqueous solution, flow rate 1.0 ml / min], and analysis by absorption at 220 nm. Has a retention time of 15.4
Min peak.
【００１３】ＭＡＬＤＩ−ＴＯＦＭＳ分析で、ｍ／ｚ＝
３４１４．２（［Ｍ＋Ｈ］+ ）に主ピークが認められ、
Ｎ２６−ＣＴ（分子式Ｃ146Ｈ241Ｏ46Ｎ44Ｓ2、平均分
子量３４１２．９）であることが確認できた。 アミノ酸分析値；Ａｓｐ ２．０５（２），Ｔｈｒ
３．７７（４），Ｓｅｒ２．７０（３），Ｇｌｕ ３．
１５（３），Ｇｌｙ ３．００（３），Ａｌａ１．０３
（１），Ｖａｌ ２．０１（２），Ｌｅｕ ５．２０
（５），Ｔｙｒ０．８５（１），Ｈｉｓ １．０２
（１），Ｌｙｓ ２．０３（２），ＮＨ3５．７１
（５），Ａｒｇ １．００（１），Ｐｒｏ ２．０３
（２），Ｃｙｓ１．７８（２）．In MALDI-TOFMS analysis, m / z =
3414.2 ([M + H] + ) with a major peak,
N26-CT (molecular formula: C 146 H 241 O 46 N 44 S 2 , average molecular weight: 3412.9) was confirmed. Amino acid analysis value; Asp 2.05 (2), Thr
3.77 (4), Ser 2.70 (3), Glu
15 (3), Gly 3.00 (3), Ala1.03
(1), Val 2.01 (2), Leu 5.20
(5), Tyr 0.85 (1), His 1.02
(1), Lys 2.03 (2), NH 3 5.71
(5), Arg 1.00 (1), Pro 2.03
(2), Cys 1.78 (2).
【００１４】[0014]
【実施例２】ＧＮ２６−ＣＴの合成 ＧＮ２６−ＣＴは、豊島ら［ Teshima, T. et al., 25-
28, in "Peptide Chemistry 1996", Kitada, C. (ed.),
Protein Research Fundation, Osaka (1997)］の方法
に従い、固相法Ｂｏｃストラテジーによって合成した。Example 2 Synthesis of GN26-CT GN26-CT was synthesized according to Teshima, T. et al., 25-
28, in "Peptide Chemistry 1996", Kitada, C. (ed.),
Protein Research Fundation, Osaka (1997)] according to the solid-phase Boc strategy.
【００１５】ＨＰＬＣ［ＯＤＳ（ＹＭＣ Ｐａｋ ＯＤ
Ｓ−ＡＭ、φ４．６×１５０ｍｍ）、展開溶媒０．１％
トリフルオロ酢酸／２０％〜７０％（２５分）アセトニ
トリル水溶液、流速１．０ｍｌ／分］で２２０ｎｍの吸
収により分析すると、生成物のＧＮ２６−ＣＴは、保持
時間１４．３分のピークとして検出された。ＭＡＬＤＩ
−ＴＯＦＭＳ分析で、ｍ／ｚ＝３６１７．４（［Ｍ＋
Ｈ］+ ）に主ピークが認められ、ＧＮ２６−ＣＴ（分子
式Ｃ154Ｈ254Ｏ51Ｎ45Ｓ2、平均分子量３６１６．２）
であることが確認できた。HPLC [ODS (YMC Pak OD)
S-AM, φ4.6 × 150mm), developing solvent 0.1%
Trifluoroacetic acid / 20% to 70% (25 minutes) acetonitrile aqueous solution, flow rate 1.0 ml / min], and the product GN26-CT was detected as a peak with a retention time of 14.3 minutes. Was. MALDI
M / z = 3617.4 ([M +
H] + ), GN26-CT (molecular formula C 154 H 254 O 51 N 45 S 2 , average molecular weight 3616.2)
It was confirmed that it was.
【００１６】アミノ酸分析値；Ａｓｐ １．９９
（２），Ｔｈｒ ３．７７（４），Ｓｅｒ２．６７
（３），Ｇｌｕ ３．１５（３），Ｇｌｙ ３．００
（３），Ａｌａ１．０４（１），Ｖａｌ ２．００
（２），Ｌｅｕ ５．３６（５），Ｔｙｒ０．９９
（１），Ｈｉｓ １．０２（１），Ｌｙｓ ２．０２
（２），ＮＨ3５．９９（５），Ａｒｇ １．００
（１），Ｐｒｏ １．９７（２），Ｃｙｓ１．７９
（２）．Amino acid analysis value; Asp 1.99
(2), Thr 3.77 (4), Ser 2.67
(3), Glu 3.15 (3), Gly 3.00
(3), Ala1.04 (1), Val2.00
(2), Leu 5.36 (5), Tyr 0.99
(1), His 1.02 (1), Lys 2.02
(2), NH 3 5.99 ( 5), Arg 1.00
(1), Pro 1.97 (2), Cys 1.79
(2).
【００１７】[0017]
【実施例３】血中カルシウム濃度低下活性測定 ［特開平７−２２８６００号（１９９５）］の試験例に
記載の方法に従って、以下のように被験物質として実施
例１、２で製造した物質及びＣＴの活性を測定した。体
重９０〜１１０ｇの健康なＳ．Ｄ．系雄性ラットを用い
た。ラットを４群に分け各群１０匹とし、次に示すよう
にエルカトニン標準品（旭化成工業（株）社製）及び被
験物質を静脈内に０．２ｍｌ投与した。Example 3 Measurement of Blood Calcium Concentration-Lowering Activity According to the method described in the test example of JP-A-7-228600 (1995), the substances prepared in Examples 1 and 2 and CT as test substances as described below were used. Was measured for activity. A healthy S. weighing 90-110 g. D. Male rats were used. The rats were divided into 4 groups, each group comprising 10 rats, and 0.2 ml of an elcatonin standard (manufactured by Asahi Kasei Kogyo KK) and a test substance were administered intravenously as shown below.
【００１８】 第１群標準品高用量（３．６ｐｍｏｌ／ｍｌ） 第２群標準品低用量（１．８ｐｍｏｌ／ｍｌ） 第３群被験物質高用量（３．６ｐｍｏｌ／ｍｌ） 第４群被験物質低用量（１．８ｐｍｏｌ／ｍｌ） 投与１時間後に、各試験動物より、採血し、血清を分離
した。原子吸光度法により血清カルシウム濃度を測定し
た。各群の血清カルシウム濃度を用いて、平行線検定法
により標準品に対する被験物質の相対力価を求めた。そ
の力価を、ＣＴの力価で割って活性比を求め、下記表１
にまとめた。Group 1 standard product high dose (3.6 pmol / ml) Group 2 standard product low dose (1.8 pmol / ml) Group 3 test substance high dose (3.6 pmol / ml) Group 4 test substance One hour after administration of the low dose (1.8 pmol / ml), blood was collected from each test animal and serum was separated. Serum calcium concentration was measured by the atomic absorption method. Using the serum calcium concentration of each group, the relative titer of the test substance to the standard was determined by a parallel line assay. The activity ratio was determined by dividing the titer by the CT titer,
Summarized in
【００１９】[0019]
【表１】 [Table 1]
【００２０】[0020]
【発明の効果】本発明は、血中カルシウム濃度低下作用
を有する新規なカルシトニン誘導体を提供する。本発明
は、医薬の分野に応用されることが期待される。The present invention provides a novel calcitonin derivative having a blood calcium concentration lowering effect. The present invention is expected to be applied to the field of medicine.
【００２１】[0021]
【配列表】 <110> Asahi Chemical Industry Co.,Ltd. <120>カルシトニン２６位誘導体 <130> X11-00299 <160> 2 <210> 1 <211> 32 <212> PRT <213>Artificial Sequence <220> <223>２６位アスパラギン酸残基をアスパラギン残基に置換したウナギ(Anguilla japonica)由来カルシトニン誘導体。 <220> <221> DISULFID <222> 1, 7 <220> <221> AMIDATION <222> 32 <400> 1 Cys Ser Asn Leu Ser Thr Cys Val Leu Gly Lys Leu Ser Gln Glu Leu 1 5 10 15 His Lys Leu Gln Thr Tyr Pro Arg Thr Asn Val Gly Ala Gly Thr Pro 20 25 30 <210> 2 <211> 32 <212> PRT <213>Artificial Sequence <220> <223>２６位アスパラギン酸残基をアスパラギン残基に置換したウナギ(Anguilla japonica)由来カルシトニン誘導体。 <220> <221> DISULFID <222> 1, 7 <220> <221> CARBOHYD <222> 26 <223>Ｎ−アセチル−Ｄ−グルコサミンが側鎖アミド基の窒素原子に結合してい る。 <220> <221> AMIDATION <222> 32 <400> 1 Cys Ser Asn Leu Ser Thr Cys Val Leu Gly Lys Leu Ser Gln Glu Leu 1 5 10 15 His Lys Leu Gln Thr Tyr Pro Arg Thr Asn Val Gly Ala Gly Thr Pro 20 25 30[Sequence List] <110> Asahi Chemical Industry Co., Ltd. <120> Calcitonin 26-position derivative <130> X11-00299 <160> 2 <210> 1 <211> 32 <212> PRT <213> Artificial Sequence < 220> <223> A calcitonin derivative derived from eel (Anguilla japonica) in which the aspartic acid residue at position 26 has been substituted with an asparagine residue. <220> <221> DISULFID <222> 1, 7 <220> <221> AMIDATION <222> 32 <400> 1 Cys Ser Asn Leu Ser Thr Cys Val Leu Gly Lys Leu Ser Gln Glu Leu 1 5 10 15 His Lys Leu Gln Thr Tyr Pro Arg Thr Asn Val Gly Ala Gly Thr Pro 20 25 30 <210> 2 <211> 32 <212> PRT <213> Artificial Sequence <220> <223> Aspartic acid residue at position 26 is replaced with an asparagine residue A calcitonin derivative derived from eel (Anguilla japonica). <220> <221> DISULFID <222> 1, 7 <220> <221> CARBOHYD <222> 26 <223> N-acetyl-D-glucosamine is bonded to the nitrogen atom of the side chain amide group. <220> <221> AMIDATION <222> 32 <400> 1 Cys Ser Asn Leu Ser Thr Cys Val Leu Gly Lys Leu Ser Gln Glu Leu 1 5 10 15 His Lys Leu Gln Thr Tyr Pro Arg Thr Asn Val Gly Ala Gly Thr Pro 20 25 30
───────────────────────────────────────────────────── フロントページの続き Ｆターム(参考） 4C084 AA07 BA02 BA09 CA18 CA21 CA45 DB31 MA66 NA03 NA14 ZA972 ZC062 4H045 AA10 BA18 BA53 CA52 DA36 EA27 FA33 HA03 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C084 AA07 BA02 BA09 CA18 CA21 CA45 DB31 MA66 NA03 NA14 ZA972 ZC062 4H045 AA10 BA18 BA53 CA52 DA36 EA27 FA33 HA03
Claims (4)
ン残基に置換したカルシトニンまたはエルカトニン誘導
体。1. A calcitonin or elcatonin derivative in which an aspartic acid residue at position 26 is substituted with an asparagine residue.
ル−Ｄ−グルコサミンが側鎖アミド基の窒素原子に結合
しているアスパラギン残基に置換したカルシトニンまた
はエルカトニン誘導体。2. A calcitonin or elcatonin derivative in which an aspartic acid residue at position 26 is substituted by an asparagine residue in which N-acetyl-D-glucosamine is bonded to a nitrogen atom of a side chain amide group.
スパラギン酸残基をアスパラギン残基に置換したウナギ
由来カルシトニン誘導体。3. An eel-derived calcitonin derivative in which the aspartic acid residue at position 26 is replaced with an asparagine residue, represented by SEQ ID NO: 1 in the sequence listing.
スパラギン酸残基をＮ−アセチル−Ｄ−グルコサミンが
側鎖アミド基の窒素原子に結合しているアスパラギン残
基に置換したウナギ由来カルシトニン誘導体。4. An eel derived from eel in which aspartic acid residue at position 26 represented by SEQ ID NO: 2 in the sequence listing is replaced by an asparagine residue in which N-acetyl-D-glucosamine is bonded to a nitrogen atom of a side chain amide group Calcitonin derivatives.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11092523A JP2000290297A (en) | 1999-03-31 | 1999-03-31 | 26 position-derivative of calcitonin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11092523A JP2000290297A (en) | 1999-03-31 | 1999-03-31 | 26 position-derivative of calcitonin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000290297A true JP2000290297A (en) | 2000-10-17 |
Family
ID=14056712
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11092523A Withdrawn JP2000290297A (en) | 1999-03-31 | 1999-03-31 | 26 position-derivative of calcitonin |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2000290297A (en) |
-
1999
- 1999-03-31 JP JP11092523A patent/JP2000290297A/en not_active Withdrawn
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|---|---|---|---|
| A300 | Withdrawal of application because of no request for examination |
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