NZ334595A - Peptide prodrugs containing an alpha-hydroxyacid linker that have increased stability against enzymatic cleavage - Google Patents

Peptide prodrugs containing an alpha-hydroxyacid linker that have increased stability against enzymatic cleavage

Info

Publication number
NZ334595A
NZ334595A NZ334595A NZ33459597A NZ334595A NZ 334595 A NZ334595 A NZ 334595A NZ 334595 A NZ334595 A NZ 334595A NZ 33459597 A NZ33459597 A NZ 33459597A NZ 334595 A NZ334595 A NZ 334595A
Authority
NZ
New Zealand
Prior art keywords
bond
peptide
alpha
enzymatic cleavage
formula
Prior art date
Application number
NZ334595A
Inventor
Bjarne Due Larsen
Arne Holm
Original Assignee
Zealand Pharmaceuticals As
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Zealand Pharmaceuticals As filed Critical Zealand Pharmaceuticals As
Publication of NZ334595A publication Critical patent/NZ334595A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
    • C07K1/1075—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of amino acids or peptide residues
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Abstract

Peptide prodrugs of the general formula (I): X-L-Z, wherein X designates a pharmaceutically active peptide sequence, e.g. Leu-enkephalin; Z designates a peptide pre-sequence of 2 to 20 amino acid units, preferably comprising lysine and glutamic acid; and L is a linking group comprising from 3 to 9 backbone atoms, wherein the bond between the C-terminal carbonyl of X and L is different from a C-N amide bond. Preferably, the bond between X and L is an ester bond. It has been found that it is possible to obtain a remarkable increase in the resistance towards degradation by proteolytic enzymes such as carboxypeptidase A, pepsin A, leucine aminopeptidase, 'alpha'-chymotrypsin when masking a pharmaceutically active peptide as a prodrug of the formula (I). The prodrugs of formula (I) are cleaved by the blood plasma enzyme butyryl cholinesterase indicating a readily bioreversibility. It is believed that the stability towards enzymatic cleavage is due to an induced helix-like structure.
NZ334595A 1996-09-09 1997-09-09 Peptide prodrugs containing an alpha-hydroxyacid linker that have increased stability against enzymatic cleavage NZ334595A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DK97296 1996-09-09
PCT/DK1997/000376 WO1998011126A1 (en) 1996-09-09 1997-09-09 Peptide prodrugs containing an alpha-hydroxyacid linker

Publications (1)

Publication Number Publication Date
NZ334595A true NZ334595A (en) 2000-08-25

Family

ID=8099572

Family Applications (1)

Application Number Title Priority Date Filing Date
NZ334595A NZ334595A (en) 1996-09-09 1997-09-09 Peptide prodrugs containing an alpha-hydroxyacid linker that have increased stability against enzymatic cleavage

Country Status (8)

Country Link
EP (1) EP0932614A1 (en)
JP (1) JP2001505872A (en)
KR (1) KR20000036015A (en)
AU (1) AU724326B2 (en)
CA (1) CA2265454A1 (en)
IL (1) IL128828A0 (en)
NZ (1) NZ334595A (en)
WO (1) WO1998011126A1 (en)

Families Citing this family (74)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU6278298A (en) * 1997-02-14 1998-09-08 Salk Institute For Biological Studies, The Methods and compositions for delivery of therapeutic agents to bone tissue employing conjugates of negatively charged peptide oligomers with therapeutic agents
JP4394279B2 (en) 1998-03-09 2010-01-06 ジーランド ファーマ アクティーゼルスカブ Pharmacologically active peptide conjugates with reduced propensity to enzymatic hydrolysis
US6528486B1 (en) 1999-07-12 2003-03-04 Zealand Pharma A/S Peptide agonists of GLP-1 activity
EP1076066A1 (en) * 1999-07-12 2001-02-14 Zealand Pharmaceuticals A/S Peptides for lowering blood glucose levels
US7671029B2 (en) 1999-08-06 2010-03-02 Immupharma Sa Compositions and methods for enhanced pharmacological activity of compositions comprising peptide drug substances
US6908900B2 (en) * 2001-01-17 2005-06-21 Zimmer & Associates Ag Compositions and methods for enhanced pharmacological activity through oral and parenteral administration of compositions comprising polypeptide drug substances and other poorly absorbed active ingredients
EP1224318A2 (en) * 1999-10-29 2002-07-24 Novus International, Inc. Oligomers and oligomeric segments of alpha-hydroxy carboxylic acids and alpha-amino acids
US6939693B2 (en) 1999-10-29 2005-09-06 Novus International, Inc. Enantioselective oligomerization of α-hydroxy carboxylic acids and α-amino acids
DE10018617A1 (en) * 2000-01-13 2001-10-31 Joerg G Moser Cyclodextrin dimers with peptide spacer structures for detoxification of active pharmaceutical ingredients with high potential for side effects
ATE513563T1 (en) 2000-10-09 2011-07-15 Isis Innovation THERAPEUTIC AND TOLERANCE-INDUCING ANTIBODIES
US6881829B2 (en) * 2002-04-26 2005-04-19 Chimeracom, L.L.C. Chimeric hybrid analgesics
BRPI0520563A2 (en) 2005-09-21 2009-05-19 7Tm Pharma As selective y4 receptor agonists for therapeutic interventions
AU2005337101A1 (en) 2005-09-21 2007-04-12 7Tm Pharma A/S Y2 selective receptor agonists for therapeutic interventions
CN101534846B (en) 2005-11-07 2014-11-05 印第安纳大学研究及科技有限公司 Glucagon analogs exhibiting physiological solubility and stability
US8669228B2 (en) 2007-01-05 2014-03-11 Indiana University Research And Technology Corporation Glucagon analogs exhibiting enhanced solubility in physiological pH buffers
AU2008216265B2 (en) 2007-02-15 2014-04-03 Indiana University Research And Technology Corporation Glucagon/GLP-1 receptor co-agonists
JP6035009B2 (en) 2007-08-22 2016-11-30 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Activable binding polypeptides and methods for identification and use thereof
CA2707861A1 (en) 2007-10-30 2009-05-07 Indiana University Research And Technology Corporation Glucagon antagonists
JP5771005B2 (en) 2007-10-30 2015-08-26 インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションＩｎｄｉａｎａ Ｕｎｉｖｅｒｓｉｔｙ Ｒｅｓｅａｒｃｈ Ａｎｄ Ｔｅｃｈｎｏｌｏｇｙ Ｃｏｒｐｏｒａｔｉｏｎ Glucagon antagonist and compound showing GLP-1 agonist activity
AU2009210570B2 (en) 2008-01-30 2014-11-20 Indiana University Research And Technology Corporation Ester-based insulin prodrugs
CN102088989B (en) 2008-06-17 2014-11-26 印第安纳大学研究及科技有限公司 Glucagon analogs exhibiting enhanced solubility and stability physiological pH buffers
PE20100255A1 (en) 2008-06-17 2010-04-25 Univ Indiana Res & Tech Corp GLUCAGON / GLP-1 RECEPTOR CO-AGONISTS
TWI474835B (en) 2008-06-17 2015-03-01 Univ Indiana Res & Tech Corp Gip-based mixed agonists for treatment of metabolic disorders and obesity
UA104605C2 (en) 2008-12-15 2014-02-25 Зіленд Фарма А/С Glucagon analogues
MX2011006320A (en) 2008-12-15 2011-09-22 Zealand Pharma As Glucagon analogues.
DK2370462T3 (en) 2008-12-15 2014-09-08 Zealand Pharma As Glucagon-ANALOGS
ES2477880T3 (en) 2008-12-15 2014-07-18 Zealand Pharma A/S Glucagon analogues
JP5789515B2 (en) 2008-12-19 2015-10-07 インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションＩｎｄｉａｎａ Ｕｎｉｖｅｒｓｉｔｙ Ｒｅｓｅａｒｃｈ Ａｎｄ Ｔｅｃｈｎｏｌｏｇｙ Ｃｏｒｐｏｒａｔｉｏｎ Insulin analogue
JP2012512903A (en) * 2008-12-19 2012-06-07 インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーション Amide glucagon superfamily peptide prodrug
WO2010080609A1 (en) 2008-12-19 2010-07-15 Indiana University Research And Technology Corporation Amide-based insulin prodrugs
JP5851842B2 (en) 2009-01-12 2016-02-03 サイトムエックス セラピューティクス, インク.CytomX Therapeutics, Inc. Modified antibody composition and methods of making and using the same
AU2010260058B2 (en) 2009-06-16 2015-09-24 Indiana University Research And Technology Corporation GIP receptor-active glucagon compounds
DK2454282T3 (en) 2009-07-13 2015-05-04 Zealand Pharma As acetylated glucagonanaloger
US8703701B2 (en) 2009-12-18 2014-04-22 Indiana University Research And Technology Corporation Glucagon/GLP-1 receptor co-agonists
CA2788304A1 (en) 2010-01-27 2011-08-04 Indiana University Research And Technology Corporation Glucagon antagonist - gip agonist conjugates and compositions for the treatment of metabolic disorders and obesity
SG184988A1 (en) 2010-04-27 2012-11-29 Zealand Pharma As Peptide conjugates of glp-1 receptor agonists and gastrin and their use
KR20130062931A (en) 2010-05-13 2013-06-13 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 Glucagon superfamily peptides exhibiting nuclear hormone receptor activity
WO2011143208A1 (en) 2010-05-13 2011-11-17 Indiana University Research And Technology Corporation Glucagon superfamily peptides exhibiting g protein-coupled receptor activity
WO2011159895A2 (en) 2010-06-16 2011-12-22 Indiana University Research And Technology Corporation Single chain insulin agonists exhibiting high activity at the insulin receptor
UY33462A (en) 2010-06-23 2012-01-31 Zealand Pharma As GLUCAGON ANALOGS
RU2580317C2 (en) 2010-06-24 2016-04-10 Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн Peptide pro-drugs of amide glucagon superfamily
EP2585102B1 (en) 2010-06-24 2015-05-06 Indiana University Research and Technology Corporation Amide-based insulin prodrugs
WO2011160633A1 (en) 2010-06-24 2011-12-29 Zealand Pharma A/S Glucagon analogues
EA201390941A1 (en) 2010-12-22 2013-12-30 Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн GLUCAGON ANALOGUES, EXPERIENCING ACTIVITY ON GIP RECEPTOR
US20140221283A1 (en) 2011-06-22 2014-08-07 Indiana University Research And Technology Corporation Glucagon/glp-1 receptor co-agonists
US9309301B2 (en) 2011-06-22 2016-04-12 Indiana University Research And Technology Corporation Glucagon/GLP-1 receptor co-agonists
WO2013024053A1 (en) * 2011-08-12 2013-02-21 Ascendis Pharma A/S Carrier-linked prodrugs having reversible carboxylic ester linkages
BR112014010780A2 (en) 2011-11-03 2017-04-25 Zealand Pharma As glp-1-gastrin receptor agonist peptide conjugates
CA2847246A1 (en) 2011-11-17 2013-05-23 Indiana University Research And Technology Corporation Glucagon superfamily peptides exhibiting glucocorticoid receptor activity
EP2793932B1 (en) 2011-12-20 2018-10-03 Indiana University Research and Technology Corporation Ctp-based insulin analogs for treatment of diabetes
IN2014MN02164A (en) 2012-04-27 2015-08-28 Cytomx Therapeutics Inc
MX356641B (en) 2012-05-03 2018-06-07 Zealand Pharma As Gip-glp-1 dual agonist compounds and methods.
ES2602486T3 (en) 2012-06-21 2017-02-21 Indiana University Research And Technology Corporation Glucagon analogs showing GIP receptor activity
NZ704043A (en) 2012-07-23 2017-07-28 Zealand Pharma As Glucagon analogues
TWI608013B (en) 2012-09-17 2017-12-11 西蘭製藥公司 Glucagon analogues
JP6387008B2 (en) 2012-09-26 2018-09-05 インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションＩｎｄｉａｎａ Ｕｎｉｖｅｒｓｉｔｙ Ｒｅｓｅａｒｃｈ Ａｎｄ Ｔｅｃｈｎｏｌｏｇｙ Ｃｏｒｐｏｒａｔｉｏｎ Insulin analog dimer
EP2926829B1 (en) 2012-11-30 2018-07-25 Glytech, Inc. Sugar chain-attached linker, compound containing sugar chain-attached linker and physiologically active substance or salt thereof, and method for producing same
US20160024169A1 (en) 2013-03-14 2016-01-28 Indiana University Research And Technology Corporation Insulin-incretin conjugates
DK2976325T3 (en) 2013-03-21 2017-06-06 Sanofi Aventis Deutschland SYNTHESIS OF PEPTIDE PRODUCTS CONTAINING CYCLIC IMID
HUE034308T2 (en) 2013-03-21 2018-02-28 Sanofi Aventis Deutschland Synthesis of hydantoin containing peptide products
CA2911542C (en) 2013-05-07 2022-06-07 Merck Patent Gmbh Peptides and peptide/active compound conjugates for renal targeting
LT2994152T (en) * 2013-05-07 2018-11-26 Merck Patent Gmbh Conjugates for protection from nephrotoxic active substances
PL3057984T3 (en) 2013-10-17 2018-12-31 Zealand Pharma A/S Acylated glucagon analogues
US9988429B2 (en) 2013-10-17 2018-06-05 Zealand Pharma A/S Glucagon analogues
WO2015066279A2 (en) 2013-10-30 2015-05-07 Cytomx Therapeutics, Inc. Activatable antibodies that bind epidermal growth factor receptor and methods of use thereof
MX369770B (en) 2013-11-06 2019-11-21 Zealand Pharma As Glucagon-glp-1-gip triple agonist compounds.
EP3065767B1 (en) 2013-11-06 2020-12-30 Zealand Pharma A/S Gip-glp-1 dual agonist compounds and methods
WO2015089283A1 (en) 2013-12-11 2015-06-18 Cytomx Therapeutics, Inc. Antibodies that bind activatable antibodies and methods of use thereof
EP3197912B1 (en) 2014-09-24 2023-01-04 Indiana University Research & Technology Corporation Lipidated amide-based insulin prodrugs
CN108271356A (en) 2014-09-24 2018-07-10 印第安纳大学研究及科技有限公司 Duodenin-insulin conjugate
CA2965732A1 (en) 2014-10-29 2016-05-06 Zealand Pharma A/S Gip agonist compounds and methods
JP6989385B2 (en) 2015-04-16 2022-01-05 ジーランド ファーマ アクティーゼルスカブ Acylated glucagon analog
JP6563614B1 (en) 2016-12-09 2019-08-21 ジーランド・ファーマ・ア／エス Acylated GLP-1 / GLP-2 dual agonist
AU2018368769A1 (en) * 2017-11-17 2020-07-02 Cytogel Pharma, Llc Polymer agonists of mu opioid receptors

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5589356A (en) * 1993-06-21 1996-12-31 Vanderbilt University Litigation of sidechain unprotected peptides via a masked glycoaldehyde ester and O,N-acyl rearrangement

Also Published As

Publication number Publication date
EP0932614A1 (en) 1999-08-04
WO1998011126A1 (en) 1998-03-19
KR20000036015A (en) 2000-06-26
JP2001505872A (en) 2001-05-08
AU724326B2 (en) 2000-09-14
CA2265454A1 (en) 1998-03-19
AU4199497A (en) 1998-04-02
IL128828A0 (en) 2000-01-31

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