Title:
STABILIZED ALPHA-HELICAL PEPTIDES
Document Type and Number:
WIPO Patent Application WO2005040202
Kind Code:
A3
Abstract:
The present invention presents modules from which helical constraints can be built by very flexible strategies. The peptide bonds involved partially compensate the hydrophobic nature of the disulfide bonds, which are also included into the constraint strategy. Thus, the invention presents solutions, by means of which peptide bonds or closure of disulfide bridges can be used alternatively for closure of the constraint. This offers greater synthetic flexibility. Moreover, the peptide bonds are more hydrophilic than disulfide bridges alone and offer the advantage of better solubility of the product in an aqueous surrounding. It is possible to attach solvation tags like glycosyl moieties, polyethylenglycol or other suitable extensions or appendices to the helical constraint structure. Usually, such a hydrophilic helical constraint structure replaces two hydrophobic amino acid side chains and thus improves pharmacologic properties of the molecule.
Inventors:
FRANK HANS-GEORG (NL)
HABERL UDO (DE)
RYBKA ANDREAS (DE)
BRACHT FRANZPETER (DE)
HABERL UDO (DE)
RYBKA ANDREAS (DE)
BRACHT FRANZPETER (DE)
Application Number:
PCT/EP2004/011719
Publication Date:
June 23, 2005
Filing Date:
October 18, 2004
Export Citation:
Assignee:
APLAGEN GMBH (DE)
FRANK HANS-GEORG (NL)
HABERL UDO (DE)
RYBKA ANDREAS (DE)
BRACHT FRANZPETER (DE)
FRANK HANS-GEORG (NL)
HABERL UDO (DE)
RYBKA ANDREAS (DE)
BRACHT FRANZPETER (DE)
International Classes:
C07C323/41; C07K14/55; (IPC1-7): C07K7/50; A61K38/12; C07K16/00; C07C237/06
Foreign References:
| US20020151473A1 | 2002-10-17 |
Other References:
PHELAN J C ET AL: "A general method for constraining short peptides to an [alpha]-helical conformation", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 1997 UNITED STATES, vol. 119, no. 3, 1997, pages 455 - 460, XP002267339, ISSN: 0002-7863
JACKSON D Y ET AL: "GENERAL APPROACH TO THE SYNTHESIS OF SHORT ALPHA-HELICAL PEPTIDES", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 113, no. 24, 1991, pages 9391 - 9392, XP001157324, ISSN: 0002-7863
YU C ET AL: "Synthesis and study of peptides with semirigid i and i + 7 side-chain bridges designed for alpha-helix stabilization.", BIOORGANIC & MEDICINAL CHEMISTRY. ENGLAND JAN 1999, vol. 7, no. 1, January 1999 (1999-01-01), pages 161 - 175, XP001157321, ISSN: 0968-0896
TAYLOR JOHN W: "The synthesis and study of side-chain lactam-bridged peptides", BIOPOLYMERS, vol. 66, no. 1, 2002, pages 49 - 75, XP002267340, ISSN: 0006-3525
RAUK A ET AL: "Glutathione radical: Intramolecular H abstraction by the thiyl radical", CANADIAN JOURNAL OF CHEMISTRY 2001 CANADA, vol. 79, no. 4, 2001, pages 405 - 417, XP009046071, ISSN: 0008-4042
HUFFMAN G W ET AL: "SUBSTRATE SPECIFICITY OF ISOPENICILLIN N SYNTHASE", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 35, no. 10, 15 May 1992 (1992-05-15), pages 1897 - 1914, XP002029802, ISSN: 0022-2623
JACKSON D Y ET AL: "GENERAL APPROACH TO THE SYNTHESIS OF SHORT ALPHA-HELICAL PEPTIDES", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 113, no. 24, 1991, pages 9391 - 9392, XP001157324, ISSN: 0002-7863
YU C ET AL: "Synthesis and study of peptides with semirigid i and i + 7 side-chain bridges designed for alpha-helix stabilization.", BIOORGANIC & MEDICINAL CHEMISTRY. ENGLAND JAN 1999, vol. 7, no. 1, January 1999 (1999-01-01), pages 161 - 175, XP001157321, ISSN: 0968-0896
TAYLOR JOHN W: "The synthesis and study of side-chain lactam-bridged peptides", BIOPOLYMERS, vol. 66, no. 1, 2002, pages 49 - 75, XP002267340, ISSN: 0006-3525
RAUK A ET AL: "Glutathione radical: Intramolecular H abstraction by the thiyl radical", CANADIAN JOURNAL OF CHEMISTRY 2001 CANADA, vol. 79, no. 4, 2001, pages 405 - 417, XP009046071, ISSN: 0008-4042
HUFFMAN G W ET AL: "SUBSTRATE SPECIFICITY OF ISOPENICILLIN N SYNTHASE", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 35, no. 10, 15 May 1992 (1992-05-15), pages 1897 - 1914, XP002029802, ISSN: 0022-2623
Download PDF:
Previous Patent: PIF PEPTIDES BIOLOGIC ACTIVITIES, SITE OF ACTION, AND THE ANTIBODY TO DETECT PIF
Next Patent: MSP-3-LIKE FAMILY OF GENES
Next Patent: MSP-3-LIKE FAMILY OF GENES