EP0862447A1 - Production de peptides d : methodes et compositions - Google Patents

Production de peptides d : methodes et compositions

Info

Publication number
EP0862447A1
EP0862447A1 EP96936413A EP96936413A EP0862447A1 EP 0862447 A1 EP0862447 A1 EP 0862447A1 EP 96936413 A EP96936413 A EP 96936413A EP 96936413 A EP96936413 A EP 96936413A EP 0862447 A1 EP0862447 A1 EP 0862447A1
Authority
EP
European Patent Office
Prior art keywords
peptide
ligand
amino acid
antibody
receptor
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.)
Withdrawn
Application number
EP96936413A
Other languages
German (de)
English (en)
Inventor
Barry Robson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Gryphon Therapeutics Inc
Original Assignee
Gryphon Sciences
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 Gryphon Sciences filed Critical Gryphon Sciences
Publication of EP0862447A1 publication Critical patent/EP0862447A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • D-peptides are made by chemical synthesis, using techniques that are well-known in the art.
  • D-peptides can be synthesized using stepwise addition of D-amino acids in a solid-phase synthesis method involving the use of appropriate protective groups.
  • Solid phase peptide synthesis techniques commonly used for L-peptides are described by Meinhofer, Hormonal Proteins and Peptides, vol. 2, (New York 1983); Kent, et al. , Ann. Rev. Biochem. , 57:957 (1988); and Bodanszky et al. , Peptide Synthesis, (2d ed. 1976), all of these references are incorporated by reference herein.
  • the D-antibodies of the invention can include a receptor, a substrate binding site on an enzyme, an epitope of a receptor that interferes with ligand binding when an antibody is bound to the receptor, a ligand binding site of a receptor, a co-factor binding site on an enzyme and a sugar binding site on a protein.
  • the D-peptides can include a ligand for a receptor, a substrate for an enzyme binding site, a peptide hormone for a receptor, a non-peptide hormone for a receptor, a neurotransmitter for a receptor, a co- factor for a co-factor binding site on an enzyme and a sugar for a sugar binding site on a protein.
  • mutations are selective and usually introduce at predetermined amino acid positions, conservative mutations, such as swapping polar amino acids for different polar amino acids, negatively charged amino acids for different negatively charged amino acids and hydrophobic amino acids for different hydrophobic amino acids.
  • conservative mutations such as swapping polar amino acids for different polar amino acids, negatively charged amino acids for different negatively charged amino acids and hydrophobic amino acids for different hydrophobic amino acids.
  • Such mutated regions be used with synthetic peptide libraries and can are preferably used with D-antibody phage display.
  • the method can also be applied to achiral ligands or receptors or molecules.
  • the method comprises using the achiral ligand, receptor or other molecule to generate an L-antibody; determining the amino acid sequence of the L-antibody or a portion thereof, such as the Fab fragment; synthesizing the corresponding D-antibody; and assaying the D-antibody for specific binding to the achiral ligand, receptor or other molecule.
  • the invention allows for all such modifications to the frame such as would normally risk loss of humanization, including reduction of size of the frame as discussed above, in the practice of phage display, and including progressive reduction of the size of the antibody frame in phage display.
  • This includes reduction in steps with enrichment by passing the cloned Fab head with randomized amino acids by phage display on progressively smaller frames, such that screening is performed at each size reduction step to retain activity.
  • too large a size reduction in a single step would risk total loss of activity due to too large a change of interactions between loop and frame.
  • This invention greatly broadens the scope of application of D-proteins by readily allowing production of biologically functional forms.
  • the invention also provides a means for more direct conversion of information in the human genome into pharmaceutical products.
  • the D-antibodies of the invention which include both D-analogs of complete antibodies as well as D-analogs of portions of antibodies, can be used in therapeutic compositions, as agonists or antagonists or catalysts.
  • the D- antibodies can be used to specifically bind target cells that express specific antigens, such as viral or bacterial antigens.
  • the invention also includes pharmaceutical compositions and methods of modulating biological conditions.
  • antibodies of the invention can be used to inhibit ligand binding to a receptor by contacting an effective amount of D-antibody to a receptor, thus blocking the ligand from binding to the receptor.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention porte sur des procédés de production et d'utilisation d'anticorps D et de peptides D. Lesdits anticorps et peptides sont des analogues de ligands ou de récepteurs pouvant se fixer spécifiquement aux peptides L, aux peptides contenant à la fois des L-aminoacides et des D-aminoacides de peptides chiraux et non chiraux non naturels, et à des composés chiraux et non chiraux non peptidiques. Lesdits peptides et anticorps résistent à la protéolyse dans l'intestin et dans le corps et sont moins immunogènes que leurs contreparties, les anticorps L et les peptides L. L'invention porte également sur leur procédé de fabrication.
EP96936413A 1995-10-10 1996-10-10 Production de peptides d : methodes et compositions Withdrawn EP0862447A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US550895P 1995-10-10 1995-10-10
US5508P 1995-10-10
US1443396P 1996-03-28 1996-03-28
US14433P 1996-03-28
PCT/US1996/016358 WO1997013522A1 (fr) 1995-10-10 1996-10-10 Production de peptides d : methodes et compositions

Publications (1)

Publication Number Publication Date
EP0862447A1 true EP0862447A1 (fr) 1998-09-09

Family

ID=26674440

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96936413A Withdrawn EP0862447A1 (fr) 1995-10-10 1996-10-10 Production de peptides d : methodes et compositions

Country Status (5)

Country Link
EP (1) EP0862447A1 (fr)
JP (1) JP2000500431A (fr)
AU (1) AU7442296A (fr)
CA (1) CA2234723A1 (fr)
WO (1) WO1997013522A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9722131D0 (en) * 1997-10-20 1997-12-17 Medical Res Council Method
CA2368839A1 (fr) * 1999-04-21 2000-10-26 Iwao Nozawa Polypeptide de forme d induisant une immunotolerance et techniques d'utilisation
EP1575991A4 (fr) 2002-07-03 2008-03-19 Bio Science International Inc Peptides comprenant des aminoacides d aromatiques et leurs methodes d'utilisation
KR101323846B1 (ko) * 2011-04-08 2013-10-31 광주과학기술원 타겟 친화도가 유지되고 안정성이 개선된 ｄ－앱타이드
ES2755104T3 (es) 2012-05-17 2020-04-21 Ra Pharmaceuticals Inc Inhibidores peptídicos y peptidomiméticos

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5079152A (en) * 1987-05-28 1992-01-07 Scripps Clinic And Research Foundation Antibody combining sites that exhibit stereoselective synthase activity, and methods using the same
US5248611A (en) * 1987-05-28 1993-09-28 Scripps Clinic And Research Foundation Stereoisomer separation method using antibody combing site-containing molecules

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9713522A1 *

Also Published As

Publication number Publication date
JP2000500431A (ja) 2000-01-18
AU7442296A (en) 1997-04-30
CA2234723A1 (fr) 1997-04-17
WO1997013522A1 (fr) 1997-04-17

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