Loading patent…
AssigneeNone recorded
InventorsMuriel Amblard, Jean Martinez, Gilbert Berge
Estimating the term…
The invention relates to nonpeptide oligomers of amino acids. The oligomers comprise —(NR′-A-CO)—O— units which represent a nonpeptide, restricted-mimetic inducer of the β turn in a dipeptide or tripeptide fragment. Said oligomers may be produced by peptide synthesis techniques, whether in solution or in the solid phase, and can be used in the synthesis of synthetic proteins or polypeptides, in which the peptide fragment(s) (is) are identical to those of the corresponding natural protein or polypeptide and whose structural fragment(s) comprise(s) a fragment of an oligomer according to the invention.
An oligomer, represented by one of the general formulae:
A method for preparing an artificial protein or an artificial polypeptide which is analogous to a natural protein or a natural polypeptide, consisting in carrying out solid-phase peptide synthesis coupling reactions, characterized in that, in the succession of reactions for coupling the α-amino acids constituting the natural polypeptide or protein, one or more α-amino acid sequences are replaced with an oligomer (I) or (I′), the length of which is equivalent to that of the α-amino acid sequence replaced.
An artificial polypeptide or protein which is analogous to a given natural polypeptide or protein, comprising one or more structuring fragments and one or more peptide fragments, characterized in that the peptide fragment(s) is (are) identical to those of the corresponding natural polypeptide or protein, and in that the structuring fragment(s) consist(s) of a fragment of an oligomer (I) or (I′), the length of which is substantially identical to that of the α-helical structuring component of the natural polypeptide or protein.
A protein analogous to hCRF (human corticotropin releasing factor), characterized in that it corresponds to one of the following formulae:
A protein analogous to hCRF (human corticotropin releasing factor), characterized in that it corresponds to the following formula:
Dependencies are inferred from the claim text.
Drawings are temporarily unavailable. Open the PDF at USPTO
No related US applications are recorded in the indexed filing history.
Backward citations are indexed for grants only.
Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof: linear peptides containing at least one abnormal peptide link
Hormones: corticotropin releasing factor [CRF]
Peptides
Term end not estimated
The present invention relates to oligomers of amino acids, to a method for the preparation thereof, to the use thereof for synthesizing artificial polypeptides and proteins, and to the artificial polypeptides and proteins obtained.
Proteins and polypeptides are polymers obtained by coupling a certain number of identical or different α-amino acids in a given order. They have many highly advantageous properties, but their structure makes them fragile and they are easily degraded.
An attempt has been made to increase the stability by replacing all or some of the α-amino acids in the sequence of a natural polypeptide or protein with β-amino acids (K. Gademan et al., Helvetica Chimica Acta Vol. 82 (1999), pp. 1-11). This substitution effectively made it possible to improve the stability, activity and structuring of the products obtained. β-amino acids are not, however, constrained entities and are close to the structures of α-amino acids.
The polymerization was carried out in solid phase using an Applied 433 automatic synthesizer, employing a Boc strategy, using:
as amino acid (II): (3S)-[amino]-5-(carbonylmethyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, hereinafter denoted H-DBT-OH, in which the amine function has been protected with a Boc group defined above,
as support resin: 2 g of MBHA.HCl resin substituted at 0.8 mmol/g with amine functions (marketed by Novabiochem).