Proline-locked stapled peptides and uses thereof

A polypeptide of Formula (P-I):

• or a salt or stereoisomer thereof;
• wherein:
• each instance of K and L, is, independently, a bond or a group consisting of one or more combinations of substituted or unsubstituted alkylene;
• substituted or unsubstituted alkenylene;
• substituted or unsubstituted alkynylene;
• substituted or unsubstituted heteroalkylene;
• substituted or unsubstituted heteroalkenylene;
• substituted or unsubstituted heteroalkynylene;
• substituted or unsubstituted heterocyclene, substituted or unsubstituted carbocyclene, substituted or unsubstituted arylene;
• substituted or unsubstituted heteroarylene;
• Ra is hydrogen;
• substituted or unsubstituted aliphatic;
• substituted or unsubstituted heteroaliphatic;
• substituted or unsubstituted aryl;
• substituted or unsubstituted heteroaryl;
• substituted or unsubstituted acyl;
• a resin;
• an amino protecting group;
• a label optionally joined by a linker, wherein the linker is a group consisting of one or more combinations of substituted or unsubstituted alkylene;
• substituted or unsubstituted alkenylene;
• substituted or unsubstituted alkynylene;
• substituted or unsubstituted heteroalkylene;
• substituted or unsubstituted heteroalkenylene;
• substituted or unsubstituted heteroalkynylene;
• substituted or unsubstituted carbocyclene;
• substituted or unsubstituted heterocyclene;
• substituted or unsubstituted arylene;
• or substituted or unsubstituted heteroarylene;
• Rb is, —RB, —ORB, —N(RB)2, or —SRB, wherein each instance of RB is, independently, hydrogen, substituted or unsubstituted aliphatic;
• 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 RB groups together form a substituted or unsubstituted 5- to 6-membered heterocyclic or heteroaromatic ring;
• each instance of Rc, is, independently, hydrogen;
• substituted or unsubstituted aliphatic;
• 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;
• cyano;
• isocyano;
• halo;
• or nitro;
• each instance of Rd is, independently, hydrogen;
• substituted or unsubstituted aliphatic;
• substituted or unsubstituted heteroaliphatic;
• substituted or unsubstituted aryl;
• substituted or unsubstituted heteroaryl;
• substituted or unsubstituted acyl;
• or an amino protecting group;
• each instance of Re is, independently, hydrogen;
• substituted or unsubstituted aliphatic;
• 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;
• cyano;
• isocyano;
• halo;
• or nitro;
• each instance of G is, independently, a natural or unnatural amino acid or a group of the formula:
• wherein:
• n is 1, 2, or 3;
• and
• each instance of R1 and R2 is independently hydrogen;
• substituted or unsubstituted aliphatic;
• 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;
• or halo, or R1 and R2 are joined to form a carbocyclic or heterocyclic ring;
• each instance of R3 and R4 is, independently, hydrogen;
• substituted or unsubstituted aliphatic;
• substituted or unsubstituted heteroaliphatic;
• a hydroxyl protecting group when attached to an oxygen atom, or an amino protecting group when attached to a nitrogen atom, or two R3 groups when attached to a nitrogen atom are joined to form a heterocyclic ring;
• each instance of XAA is, independently, a natural or unnatural amino acid;
• j is, independently, an integer between 1 to 10, inclusive;
• each instance of p is, independently, 1 or 2;
• each instance of v is, independently, 0 or 1;
• each instance of w and z is, independently, an integer between 0 and 100, inclusive;
• each instance of x is, independently, 1, 2, or 3;
• y is, independently, 1, 2, 3, or 4;
• and
• corresponds to a double or triple bond.