Peptoids incorporating chemoselective functionalities
AssigneeChiron Corporation
InventorsThomas Horn, Ronald N. Zuckermann
Life of this patent
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Abstract
Molecules having potential biological activity, particularly peptoids, that are conjugated to solid phase supports, spacer groups, and/or ligation moieties, and methods of their preparation, are described. In some instances, the molecules of the invention are made entirely by solid phase synthesis. In other instances, the spacer groups are hydrophilic and compositions containing them, and to solid phase synthesis of varied structure peptoids using chemoselective ligation moieties.
Claims28
A method of attaching a spacer group to a molecule selected from a peptoid, a peptide, an oligonucleotide, and an oligosaccharide, the method comprising:
- synthesizing said spacer group, via initial reaction with an amine, hydroxyl or thiol group of said molecule, by repeating alternating addition of (i) a submonomer consisting of acrylic acid, an alkanoic acid bearing a terminal leaving group, or an activated derivative thereof, and (ii) a submonomer consisting of an alkanethiol having a terminal primary amine, hydroxyl or thiol group.
A method of attaching a spacer group to a molecule selected from a peptoid, a peptide, an oligonucleotide, and an oligosaccharide, the method comprising:
- synthesizing said spacer group, via initial reaction with an amine, hydroxyl or thiol group of said molecule, by repeating alternating addition of (i) a submonomer consisting of acrylic acid, an alkanoic acid bearing a terminal leaving group, or an activated derivative thereof, and (ii) a submonomer consisting of an alkanethiol having a terminal primary amine, hydroxyl or thiol group:
- and
- wherein said molecule is attached to a solid phase support.
A method of attaching a spacer group to a molecule selected from a peptoid, a peptide, an oligonucleotide, and an oligosaccharide, the method comprising:
- synthesizing said spacer group, via initial reaction with an amine, hydroxyl or thiol group of said molecule, by repeating alternating addition of (i) a submonomer consisting of acrylic acid, an alkanoic acid bearing a terminal leaving group, or an activated derivative thereof, and (ii) a submonomer consisting of an alkanethiol having a terminal primary amine, hydroxyl or thiol group:
- and
- wherein said molecule is attached to a solid phase support and said molecule is synthesized on said solid phase support.
A method of attaching a spacer group to a molecule selected from a peptoid, a peptide, an oligonucleotide, and an oligosaceharide, the method comprising:
- synthesizing said spacer group, via initial reaction with an amine, hydroxyl or thiol group of said molecule, by repeating alternating addition of (i) a submonomer consisting of acrylic acid, an alkanoic acid bearing a terminal leaving group, or an activated derivative thereof, and (ii) a submonomer consisting of an alkanetbiol having a terminal primary amine, hydroxyl or thiol group;
- and
- further comprising converting sulfide linkages in said spacer group to sulfoxide linkages.
A method of attaching a spacer group to a molecule selected from a peptoid, a peptide, an oligonucleotide, and an oligosaccharide, having a acrylamide group at a terminus, the method comprising:
- synthesizing said spacer group, via initial reaction with said acrylamide, by repeating the steps of (i) reacting the thiol functionality of a hydroxyalkanethiol with said terminus of the molecule;
- and (ii) converting the hydroxyl functionality of the reacted hydroxyalkanethiol to a leaving group.
A method of preparing a spacer-molecule conjugate on a solid support, said molecule selected from a peptoid, a peptide, an oligonucleotide, and an oligosaccharide, the method comprising:
- (a) synthesizing a spacer group on an amine- or hydroxyl-derivatized solid support, by repeating alternating addition of (i) a submonomer consisting of acrylic acid, an alkanoic acid bearing a terminal leaving group, or an activated derivative thereof, and (ii) a submonomer consisting of an alkanethiol having a terminal primary amine, hydroxyl or thiol group;
- and
- (b) attaching said molecule to said spacer.
A method of preparing a spacer-peptoid conjugate on a solid support, comprising:
- synthesizing a spacer group on an amine- or hydroxyl-derivatized solid support, by repeating alternating addition of (i) a submonomer consisting of acrylic acid, an alkanoic acid bearing a terminal leaving group, or an activated derivative thereof, and (ii) a submonomer consisting of an alkanethiol having a terminal primary amine, hydroxyl or thiol group;
- and
- synthesizing the peptoid, attached to an amino, hydroxyl or thiol group of said spacer, by repeating alternating addition of (i) an acyl submonomer bearing an α-leaving group and (ii) a primary amine submonomer.
A method of preparing a spacer-molecule conjugate on a solid support, said molecule selected from a peptoid, a peptide, an oligonucleotide, and an oligosaccharide, the method comprising:
- (a) synthesizing a spacer group on an amine- or hydroxyl-derivatized solid support, by repeating alternating addition of (i) a submonomer consisting of acrylic acid, an alkanoic acid bearing a terminal leaving group, or an activated derivative thereof, and (ii) a submonomer consisting of an alkanethiol having a terminal primary amine, hydroxyl or thiol group;
- (b) attaching said molecule to said spacer;
- and
- wherein said solid support is a planar array comprising a plurality of spacer groups, and said molecule comprises a plurality of different-sequence peptoids attached to said spacer groups.
A method of preparing a spacer-molecule conjugate on a solid support, said molecule selected from a peptoid, a peptide, an oligonucleotide, and an oligosaccharide, the method comprising:
- (a) synthesizing a spacer group on an amine- or hydroxyl-derivatized solid support, by repeating alternating addition of (I) a submonomer consisting of acrylic acid, an alkanoic acid bearing a terminal leaving group, or an activated derivative thereof, and (ii) a submonomer consisting of an alkanethiol having a terminal primary amine, hydroxyl or thiol group;
- (b) attaching said molecule to said spacer;
- and
- wherein said solid support is a plurality of beads, and said peptoid synthesizing comprises synthesizing a plurality of different-sequence peptoids attached to said beads, wherein each bead contains same-sequence peptoids.
A method of preparing a spacer-molecule conjugate on a solid support, said molecule selected from a peptoid, a peptide, an oligonucleotide, and an oligosaccharide, the method comprising:
- (a) synthesizing a spacer group on an acrylamide-derivatized solid support, by (i) reacting the thiol functionality of a hydroxyalkanethiol with said acrylamide;
- and repeating the steps of:
- (ii) converting the hydroxyl functionality of the reacted hydroxyalkanethiol to a leaving group, and (iii) reacting the thiol functionality of a hydroxyalkanethiol with said leaving group;
- and
- (b) attaching said molecule to said spacer.
Dependencies are inferred from the claim text.