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US 8,592,377 B2Granted
Stitched polypeptides
AssigneePresident and Fellows of Harvard College
InventorsGregory L. Verdine, Young-Woo Kim
Life of this patent
Estimating the term…
Abstract
The present invention provides inventive stitched polypeptides, pharmaceutical compositions thereof, and methods of making and using inventive stitched polypeptides.
Claims33
A substantially alpha-helical polypeptide of the formula:
- or a pharmaceutically acceptable salt thereof;
- wherein:
- each instance of K, L1, L2, and M is, independently, a cyclic or acyclic, branched or unbranched, substituted or unsubstituted C1-8 alkylene;
- each instance of Ra is, independently, hydrogen;
- a cyclic or acyclic, branched or unbranched, substituted or unsubstituted aliphatic;
- a cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroaliphatic;
- a substituted or unsubstituted aryl;
- a substituted or unsubstituted heteroaryl;
- a cyclic or acyclic, substituted or unsubstituted acyl;
- or Ra is a suitable amino protecting group;
- each instance of Rb is hydrogen or cyclic or acyclic, branched or unbranched, substituted or unsubstituted aliphatic;
- each instance of Re is, independently, —RE, —ORE, —N(RE)2, or —SRE, wherein each instance of RE is, independently, hydrogen;
- a cyclic or acyclic, branched or unbranched, substituted or unsubstituted aliphatic;
- a cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroaliphatic;
- a substituted or unsubstituted aryl;
- a substituted or unsubstituted heteroaryl;
- a substituted or unsubstituted acyl;
- a resin;
- a suitable hydroxyl, amino, or thiol protecting group;
- or two RE groups together form a 5- to 6-membered heterocyclic or heteroaromatic ring;
- each instance of Rf is, independently, hydrogen;
- a cyclic or acyclic, branched or unbranched, substituted or unsubstituted aliphatic;
- a cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroaliphatic;
- a substituted or unsubstituted aryl;
- a substituted or unsubstituted heteroaryl;
- a substituted or unsubstituted acyl;
- a resin;
- a suitable amino protecting group;
- a label optionally joined by a linker, wherein the linker is selected from cyclic or acyclic, branched or unbranched, substituted or unsubstituted alkylene;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted alkenylene;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted alkynylene;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroalkylene;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroalkenylene;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroalkynylene;
- substituted or unsubstituted arylene;
- substituted or unsubstituted heteroarylene;
- or substituted or unsubstituted acylene;
- or Rf and Ra together form a 5- to 6-membered heterocyclic or heteroaromatic ring;
- each instance of RKL, RLL, and RLM, is, independently, hydrogen;
- a cyclic or acyclic, branched or unbranched, substituted or unsubstituted aliphatic;
- a cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroaliphatic;
- substituted or unsubstituted aryl;
- substituted or unsubstituted heteroaryl;
- substituted or unsubstituted acyl;
- substituted or unsubstituted hydroxyl;
- substituted or unsubstituted thiol;
- substituted or unsubstituted amino;
- azido;
- cyano;
- isocyano;
- halo;
- or nitro;
- each instance of XAA is, independently, an alpha-amino acid;
- each instance of y and z is, independently, an integer from 2 to 6;
- each instance of j is, independently, an integer from 1 to 10;
- each instance of p is, independently, an integer from 0 to 10;
- each instance of s and t is, independently, an integer from 0 and 100;
- each instance of u, v, and q, is independently, an integer from 0 to 4;
- and
- corresponds to a single, double, or triple bond.
57 more elements
An alpha-helical polypeptide of the formula:
- or a pharmaceutically acceptable salt thereof;
- wherein:
- each instance of L1 and L2 is independently a straight chain alkylene of 3 to 7 carbon atoms;
- each instance of K and M is independently, a straight chain alkylene of 1 to 7 carbon atoms;
- each instance of Ra is hydrogen or alkyl of 1 to 6 carbon atoms or acyl;
- each instance of Rb is hydrogen or cyclic or acyclic, branched or unbranched, substituted or unsubstituted aliphatic;
- each instance of Re is, independently, —RE, —ORE, —N(RE)2or —SRE, wherein each instance of RE is, independently, hydrogen, cyclic or acyclic, branched or unbranched, substituted or unsubstituted aliphatic;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroaliphatic;
- substituted or unsubstituted aryl;
- substituted or unsubstituted heteroaryl;
- substituted or unsubstituted acyl;
- a resin;
- a suitable hydroxyl, amino, or thiol protecting group;
- or two RE groups together form a substituted or unsubstituted 5- to 6-membered heterocyclic or heteroaromatic ring;
- each instance of Rf is, independently, hydrogen;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted aliphatic;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroaliphatic;
- substituted or unsubstituted aryl;
- substituted or unsubstituted heteroaryl;
- substituted or unsubstituted acyl;
- a resin;
- a suitable amino protecting group;
- a label optionally joined by a linker, wherein the linker is selected from cyclic or acyclic, branched or unbranched, substituted or unsubstituted alkylene;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted alkenylene;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted alkynylene;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroalkylene;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroalkenylene;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroalkynylene;
- substituted or unsubstituted arylene;
- substituted or unsubstituted heteroarylene;
- or substituted or unsubstituted acylene;
- or Rf and Ra together form a substituted or unsubstituted 5- to 6-membered heterocyclic or heteroaromatic ring;
- each instance of XAA is, independently, an alpha-amino acid;
- each instance of y and z is, independently, an integer from 2 to 6;
- j is, an integer between 1 to 10;
- each instance of p is, independently, an integer between 0 to 10 inclusive;
- RKL, RLL and RLM are independently hydrogen;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted aliphatic;
- cyclic or acyclic, branched or unbranched, substituted or unsubstituted heteroaliphatic;
- substituted or unsubstituted aryl;
- substituted or unsubstituted heteroaryl;
- substituted or unsubstituted acyl;
- substituted or unsubstituted hydroxyl;
- substituted or unsubstituted thiol;
- substituted or unsubstituted amino;
- azido;
- cyano;
- isocyano;
- halo;
- or nitro;
- each instance of s and t is, independently, an integer from 0 to 100;
- u, v, and q, are independently an integer from 0 to 4;
- corresponds to a single, double or triple bond.
50 more elements
Dependencies are inferred from the claim text.