JP2008504237A - ペプチド系化合物 - Google Patents
ペプチド系化合物 Download PDFInfo
- Publication number
- JP2008504237A JP2008504237A JP2007516412A JP2007516412A JP2008504237A JP 2008504237 A JP2008504237 A JP 2008504237A JP 2007516412 A JP2007516412 A JP 2007516412A JP 2007516412 A JP2007516412 A JP 2007516412A JP 2008504237 A JP2008504237 A JP 2008504237A
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- ILRYLPWNYFXEMH-UHFFFAOYSA-N cystathionine Chemical compound OC(=O)C(N)CCSCC(N)C(O)=O ILRYLPWNYFXEMH-UHFFFAOYSA-N 0.000 description 1
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- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0056—Peptides, proteins, polyamino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0032—Methine dyes, e.g. cyanine dyes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70546—Integrin superfamily
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0815—Tripeptides with the first amino acid being basic
- C07K5/0817—Tripeptides with the first amino acid being basic the first amino acid being Arg
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/12—Cyclic peptides with only normal peptide bonds in the ring
- C07K5/126—Tetrapeptides
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/531—Production of immunochemical test materials
- G01N33/532—Production of labelled immunochemicals
- G01N33/533—Production of labelled immunochemicals with fluorescent label
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
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- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
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- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Gastroenterology & Hepatology (AREA)
- Microbiology (AREA)
- Zoology (AREA)
- Food Science & Technology (AREA)
- Toxicology (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
【選択図】 なし
Description
式中、Aは次の式(VIb)で表され、
Ra−C(=O)−X1−X2−X3−G−D−X4−X5−X6−X7 (VIb)
ZはAのX1、X6又はX7の1個以上と適宜スペーサー基を介して結合した1以上のシアニン色素を表す。
X3、G及びDは既に定義した通りである。
Raは、X2、X4又はX6のいずれかと結合した架橋の一部をなす−(CH2)n−基又は−(CH2)n−C6H4−基を表し、nは1〜10の正の整数を表す。
X1は結合又は1、2、3、4若しくは5個のアミノ酸残基を表し、1個以上のアミノ酸残基は適宜スペーサー部分で官能化され、好ましくは、該アミノ酸残基は酸又はアミン基のような官能性側鎖を有していて、好ましくはアスパラギン酸、グルタミン酸、ホモリシン、リシン又はジアミノプロピオン酸のようなジアミノアルキル酸から選択される。
X2及びX4は各々独立に環化架橋を形成し得るアミノ酸残基、例えばジスルフィド又はチオエーテル結合を形成するシステインやホモシステイン残基、その他アスパラギン酸やリシンのように環化架橋を形成し得るアミノ酸残基を表す。好ましくは、X2及びX4はシステイン又はホモシステインの残基を表し、好ましくはX2及びX4は互いに又はRa若しくはX6と環化架橋を形成する。
X5は疎水性アミノ酸又はその誘導体を表し、好ましくはチロシン、フェニルアラニン、3−ヨード−チロシン又はナフチルアラニン残基、さらに好ましくはフェニルアラニン又は3−ヨード−チロシン残基を表す。
X6は環化架橋を形成し得るアミノ酸残基、好ましくはチオール含有アミノ酸残基、好ましくはシステイン又はホモシステイン残基を表し、好ましくはX6はRa、X2又はX4と環化架橋を形成する。
X7はスペーサー又はバイオモディファイヤー部分であるか存在せず、好ましくは単分散ポリエチレングリコール(PEG)構成単位を1〜10単位含むものであり、バイオモディファイヤーは薬剤の薬物動態及び血液クリアランス速度を変化させる機能を有する。また、X7は1〜10個のアミノ酸残基を表すものでもよく、好ましくはグリシン、リシン、アスパラギン酸又はセリンを含む。また、X7はアミノ酸残基とPEG様構造を共に含むスペーサー又はバイオモディファイアー、好ましくはビスアミノエチルエチレングリコールグリシンの組合せであってもよい。好ましい実施形態では、X7は単分散PEG様構造の式(X)の17−アミノ−5−オキソ−6−アザ−3,9,12,15−テトラオキサヘプタデカン酸からなる単位を表す。
RaとX6の間及びX2とX4の間(ネステッド立体配置を形成)、
RaとX2の間及びX4とX6の間(離散立体配置)、
RaとX4の間及びX2とX6の間(交差立体配置を形成)。
X′1は、酸又はアミン基のような官能性側鎖を有するアミノ酸残基を表し、該アミノ酸は好ましくはアスパラギン酸、グルタミン酸、ホモリシン又はリシン若しくはジアミノプロピオン酸のようなジアミノアルキル酸から選択され、さらに好ましくはアスパラギン酸又はリシンである。
X′2、X′4及びX′6はシステイン又はホモシステインのようにジスルフィド又はチオエーテル結合を形成するアミノ酸残基を表すが、ここではジスルフィド及びチオエーテル結合を示す。
W1はスペーサー部分であるか存在せず、好ましくはグルタル酸及び/又はコハク酸及び/又はポリエチレングリコール系単位から誘導されるもので、シアニン色素レポーターをペプチドに連結する。その他の代表的なスペーサー(W1)要素としては、構造型の多糖類、貯蔵型の多糖類、ポリアミノ酸及びそのメチル及びエチルエステル、ポリペプチド、オリゴ糖及びオリゴヌクレオチドが挙げられ、酵素切断部位を含んでいても含んでいなくてもよい。スペーサー部分W1の役割は、ペプチド成分の受容体結合ドメインから比較的嵩高い色素を離隔することである。
hは1又は2の正の整数である。
また、シアニン色素を表すZ基が少なくとも1つ存在する。
X′2、X′4及びX′6は好ましくは各々独立にシステイン又はホモシステイン残基を表す。
X3は好ましくはアルギニンを表す。
X5は好ましくはチロシン、フェニルアラニン、3−ヨード−チロシン又はナフチルアラニン、さらに好ましくはフェニルアラニン又は3−ヨード−チロシンを表す。
X7及びW1は式VIbで定義した通りである。好ましくは、X7は1〜10単位の単分散PEG構成単位を含むか、或いは存在せず、W1は好ましくは存在しない。
以下に示すペプチドAsp−Cys−Arg−Gly−Asp−Cys−Phe−Cysを含むペプチド化合物は、アミノ官能化シアニン色素とアスパラギン酸(X1)との結合又はシアニン色素NHSエステルとX7に位置するアミノ−PEGとの反応によって、シアニン色素に結合させることができる。
TSTU:O−(N−スクシンイミジル)−N,N,N′,N′−テトラメチルウロニウムテトラフルオロホウ酸塩
TFA:トリフルオロ酢酸
DMF:N,N−ジメチルホルムアミド
NMM:N−メチルモルホリン
実施例1:Cys2−6;c[CH 2 CO−Lys(Cy5モノ−SO 3 )−Cys−Arg−Gly−Asp−Cys−Phe−Cys]−(PEG)n−NH 2 (n=1)の合成
“Protein−Ligand Interactions: Hydrodynamics and calorimetry”, edited by Stephen E. Harding and Babur Z. Chowdhry, Oxford University Press, published 2001, chapter 2 by Bent Honore, Department of Medical Biochemisty, University of Aarhusに記載の平衡透析及び速度透析によって、色素コンジュゲートのタンパク結合分析を実施した。
Claims (18)
- ペプチドベクターと1以上のシアニン色素を含む化合物又はその生理学的に許容される塩であって、ペプチドベクターがアミノ酸配列X3−G−Dを含んでいて、ペプチドベクターとシアニン色素が連結している化合物又はその生理学的に許容される塩。
式中、X3はアルギニン、N−メチルアルギニン又はアルギニン模倣体を表し、Gはグリシンを表し、Dはアスパラギン酸を表す。 - 1以上のシアニン色素が各々スルホン酸基を2又は1個しか或いは全く含まない、請求項1記載の化合物。
- 1以上のシアニン色素が、カルバシアニン、オキサシアニン、チアシアニン及びアザシアニンからなる群から選択される、請求項1又は請求項2記載の化合物。
- 1以上のシアニン色素がカルバシアニン色素である、請求項1乃至請求項3のいずれか1項記載の化合物。
- 2つの環化架橋を含んでいて次の式(VIa)で表される、請求項1乃至請求項4のいずれか1項記載の化合物。
A−Z (VIa)
Aは次の式(VIb)で表され、
Ra−C(=O)−X1−X2−X3−G−D−X4−X5−X6−X7 (VIb)
ZはAのX1、X6又はX7の1個以上と結合した1以上のシアニン色素を表し、
X3、G及びDは前記で定義した通りであり、
Raは、X2、X4又はX6のいずれかと結合した架橋の一部をなす−(CH2)n−基又は−(CH2)n−C6H4−基を表し、nは1〜10の正の整数を表し、
X1は結合又は1、2、3、4若しくは5個のアミノ酸残基を表し、1個以上のアミノ酸残基が適宜スペーサー部分で官能化されているか、或いはアミノ酸残基は酸又はアミン基のような官能性側鎖を有し、
X2及びX4は各々独立に環化架橋を形成し得るアミノ酸残基を表し、
X5は疎水性アミノ酸又はその誘導体を表し、
X6は環化架橋を形成し得るアミノ酸残基を表し、
X7はスペーサー又はバイオモディファイヤー部分であるか、或いは存在しない。 - 以下のいずれかの式から選択される、請求項5記載の化合物。
X′1は、
酸又はアミン基のような官能性側鎖を有するアミノ酸残基を表し、該アミノ酸は、好ましくはアスパラギン酸、グルタミン酸、ホモリシン又はリシン若しくはジアミノプロピオン酸のようなジアミノアルキル酸から選択され、さらに好ましくはアスパラギン酸又はリシンであり、
X′2、X′4及びX′6は、ジスルフィド結合又はチオエーテル結合を形成するアミノ酸残基を表し、
W1はスペーサー部分であるか、或いは存在せず、
hは1又は2の正の整数であり、
シアニン色素を表すZ基が少なくとも1つ存在する。 - Raが−(CH2)−を表す、請求項6記載の式VIIの化合物。
- X′1が酸又はアミン基のような官能性側鎖を有するアミノ酸残基を表し、該アミノ酸がアスパラギン酸、グルタミン酸、ホモリシン、リシン、又はジアミノプロピオン酸から選択される、請求項6又は請求項7記載の式VIIの化合物。
- X′2、X′4及びX′6が各々独立にシステイン残基又はホモシステイン残基を表す、請求項6乃至請求項8のいずれか1項記載の式VIIの化合物。
- X3がアルギニンを表す、請求項6乃至請求項9のいずれか1項記載の式VIIの化合物。
- X5がフェニルアラニン、チロシン、3−ヨード−チロシン又はナフチルアラニンを表す、請求項6乃至請求項10のいずれか1項記載の式VIIの化合物。
- X7が1〜10単位の単分散PEG構成単位を含むか、或いは存在しない、請求項6乃至請求項11のいずれか1項記載の式VIIの化合物。
- シアニン色素Zが、X′1、W1、X6又はX7の1以上とアミド結合、スルホンアミド結合又はチオエーテル結合を介して結合している、請求項6乃至請求項12のいずれか1項記載の化合物。
- 請求項1乃至請求項13のいずれか1項記載の化合物の有効量を、1種以上の薬学的に許容される補助剤、賦形剤又は希釈剤と共に含んでなる医薬組成物。
- 光学イメージング用造影剤として使用するための、請求項1乃至請求項13のいずれか1項記載の化合物。
- 造影剤をヒト又は動物の身体に投与してヒト又は動物の身体の少なくとも一部分の画像を生成させる診断法に用いられる光学イメージング用造影剤の製造における、請求項1乃至請求項13のいずれか1項記載の化合物の使用。
- 造影剤をヒト又は動物の身体に投与して造影剤が分配された身体の少なくとも一部分の画像を生成させる光学イメージングによるヒト又は動物の身体の画像生成方法であって、該造影剤が請求項1乃至請求項13のいずれか1項記載の化合物を含むことを特徴とする方法。
- 血管新生に関連した病態に対処するための薬剤によるヒト又は動物の身体の治療効果をモニタリングする方法であって、請求項1乃至請求項14のいずれか1項記載の化合物又は組成物を身体に投与し、細胞受容体による上記化合物又は組成物の取り込みを検出し、任意ではあるが好ましくは、上記投与と検出を、例えば上記化合物又は組成物による治療の前後途中のいずれかに繰り返すことを含む方法。
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AU2005307195A1 (en) * | 2004-11-22 | 2006-05-26 | Ge Healthcare As | Contrast agents to target extracellular matrix |
ITMI20050328A1 (it) | 2005-03-03 | 2006-09-04 | Univ Degli Studi Milano | Composti peptidomimetrici e preparazione di derivati biologicamente attivi |
GB0718967D0 (en) * | 2007-09-28 | 2007-11-07 | Ge Healthcare Ltd | Peptide imaging agents |
GB0718957D0 (en) * | 2007-09-28 | 2007-11-07 | Ge Healthcare Ltd | Optical imaging agents |
US20100291706A1 (en) * | 2009-05-15 | 2010-11-18 | Millipore Corporation | Dye conjugates and methods of use |
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WO2014013730A1 (en) | 2012-07-20 | 2014-01-23 | Canon Kabushiki Kaisha | Compound and photoacoustic imaging contrast medium containing the compound |
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001077145A2 (en) * | 2000-04-12 | 2001-10-18 | Amersham Health As | Integrin binding peptide derivatives |
JP2002012782A (ja) * | 1994-12-07 | 2002-01-15 | Inst Fuer Diagnostikforschung Gmbh An Der Freien Univ Berlin | 生体内診断剤に適する化合物 |
WO2003006491A2 (en) * | 2001-07-10 | 2003-01-23 | Amersham Health As | Peptide-based compounds for targeting intergin receptors |
Family Cites Families (1)
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-
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002012782A (ja) * | 1994-12-07 | 2002-01-15 | Inst Fuer Diagnostikforschung Gmbh An Der Freien Univ Berlin | 生体内診断剤に適する化合物 |
WO2001077145A2 (en) * | 2000-04-12 | 2001-10-18 | Amersham Health As | Integrin binding peptide derivatives |
WO2003006491A2 (en) * | 2001-07-10 | 2003-01-23 | Amersham Health As | Peptide-based compounds for targeting intergin receptors |
Non-Patent Citations (1)
Title |
---|
JPN7011000699; Cyanine fluorescent dyes for life science research , 1995 * |
Cited By (2)
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JP2011519348A (ja) * | 2008-03-14 | 2011-07-07 | ビセン メディカル, インコーポレイテッド | インテグリン標的化剤およびそれらを用いるinvivoおよびinvitroでの画像化方法 |
JP2014058556A (ja) * | 2008-03-14 | 2014-04-03 | Visen Medical Inc | インテグリン標的化剤およびそれらを用いるinvivoおよびinvitroでの画像化方法 |
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