Templated molecules and methods for using such molecules

• US 9,688,980 B2
• Filed: 12/16/2014
• Issued: 06/27/2017
• Est. Priority Date: 06/20/2001
• Status: Expired due to Term

• Current Assignee: Nuevolution A/S (Amgen Inc.)
• Original Assignee: Nuevolution A/S (Amgen Inc.)
• Inventors: Pedersen, Henrik, Gouliaev, Alex Haahr, Olsen, Eva Kampmann, Felding, Jakob, Godskesen, Michael Anders, Glad, Sanne Schroder, Thisted, Thomas, Holtmann, Anette, Franch, Thomas, Sams, Christian Klarner, Slok, Frank Abilgaard, Husemoen, Gitte Nystrup, Norregaard-Madsen, Mads, Freskgard, Per-Ola, Hyldtoft, Lene
• Primary Examiner(s): Riley, Jezia
• Application Number:
  US14/571,941
• Publication Number:
  US 20150315567A1
• Time in Patent Office: 924 Days
• Field of Search: 506 16, 506 18
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07H 23/00 Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12 esters with inorganic acids C07H11/00; metal salts, see parent compounds
• CPC Class Codes: C12N 15/1058 Directional evolution of libraries, e.g. evolution of libraries is achieved by mutagenesis and screening or selection of mixed population of organisms
• CPC Class Codes: C12N 15/1068 Template (nucleic acid) mediated chemical library synthesis, e.g. chemical and enzymatical DNA-templated organic molecule synthesis, libraries prepared by non ribosomal polypeptide synthesis [NRPS], DNA/RNA-polymerase mediated polypeptide synthesis
• CPC Class Codes: C12P 19/34 Polynucleotides, e.g. nucleic acids, oligoribonucleotides
• CPC Class Codes: C40B 40/00 Libraries per se, e.g. arrays, mixtures

Abstract

The present invention relates to a method for synthesising templated molecules. In one aspect of the invention, the templated molecules are linked to the template which templated the synthesis thereof. The intion allows the generation of libraries which can be screened for e.g. therapeutic activity.

Claims

1. A composition of more than 10³ different cyclic molecules each comprising a plurality of covalently linked amino acid residues and a polynucleotide identifying the cyclic molecule, each cyclic molecule being covalently linked by means of a covalent linker to said polynucleotide.

2. The composition according to claim 1, wherein the polynucleotide is a double stranded polynucleotide.

3. The composition according to claim 1, wherein the cyclic molecule is selected from the group consisting of α

-peptides, β

-peptides, γ

-peptides and 107 -peptides.

4. The composition according to claim 1, wherein the covalently linked, amino acid residues are selected from natural amino acids and non-natural amino acids, including a combination of both.

5. The composition according to claim 1, wherein the cyclic molecule comprises amino acids selected from the group consisting of α

-amino acids, β

-amino acids, γ

-amino acids and ω

-amino acids.

6. The composition according to claim 1, wherein the covalently linked, amino acid residues form a peptide having more than one portion, wherein at least one portion of the peptide is selected from the group consisting of an α

-peptide portion, a β

-peptide portion, a γ

-peptide portion, and a 107 -peptide portion.

7. The composition according to claim 1, wherein the cyclic molecule comprises L-form amino acids and D-form amino acids.

8. The composition according to claim 1, wherein the cyclic molecule and the polynucleotide identifying said cyclic molecule are linked by a single linker.

9. The composition according to claim 1, wherein the cyclic molecule contains from 2 to 10 amino acid residues.

10. The composition according to claim 1, wherein the cyclic molecule contains from 3 to 8 amino acid residues.

11. The composition according to claim 1, wherein the cyclic molecule contains from 4 to 6 amino acid residues.

12. The composition according to claim 1, wherein the cyclic molecule is a monofunctional, difunctional, trifunctional or polyfunctional heterocycle.

13. The composition according to claim 1, wherein the cyclic molecule is a monocyclic, bicyclic, tricyclic or polycyclic heterocycle.

14. The composition according to claim 1, wherein the cyclic molecule is a bridged, polycyclic heterocycle.