Biologically active molecules, conjugates thereof, and therapeutic uses

A compound of the following formula

• wherein:
• L is a Ligand capable of binding to a cell or cell population;
• a is an integer from 1 to 10;
• Z2 is represented by the following structural formula:
• —Z2A-Z2B—Z2C—Z2D—, wherein Z2A, Z2B, Z2C, and Z2D are each independently absent, an amino acid residue, a peptide residue having 2-20 amino acid residues, an -alkylene-, an -alkynylene-, an -alkenylene-, a -cycloalkylene-, an-arylene-, a -heteroarylene-, a -heterocyclylene-, —CR5R6—, —O—, —C(═O)—, —O—C(═O)—, —C(═O)—O—, —O—C(═O)—O—, —C(═O)—(CHx)p1—, —C(═O)—O—(CHx)p1—, —(CHx)p1—C(═O)—, —(CHx)p1—C(═O)—O—, —(O—(CH2)p2—)p3—, —((CH2)p2—O—)p3—, —C(═S)—, —C(═S)—S—, —C(═S)—NH—, —S—C(═S)—, —S—C(═S)—S—, —S—, —SO—, —SO2—, —NR4—, —N(R4)—C(═O)—N(R8)—, —N(R4)—C(═O)O—, —N(R4)—C(═O)—, —C(═O)—N(R4)—, —C(═O)—N(R4)—C(═O)—, —O—C(═O)—N(R4)—, —O—C(═S)—N(R4)—, —C(═S)—N(R4)—, or
• and combinations thereof or residues thereof;
• A is a natural or non-natural amino acid residue, or a peptide residue comprising 2-20 amino acid residues;
• W is —O—, —S—, —CR5R6—, or —NR4—;
• X is -arylene-, -heteroarylene-, -cycloalkylene-, or -heterocyclylene-, wherein-arylene-, -heteroarylene-, -cycloalkylene-, and -heterocyclylene- are optionally substituted;
• wherein A1 and R1 are each independently an amino acid residue, a peptide residue having 2-20 amino acid residues, an -alkylene-, an -alkynylene-, an -alkenylene-, a -cycloalkylene-, an -arylene-, a -heteroarylene-, a -heterocyclylene-, —CR5R6—, —O—, —C(═O)—, —O—C(═O)—, —C(═O)—O—, —O—C(═O)—O—, —C(═O)—(CHx)p1—, —C(═O)—O—(CHx)p1—, —(CHx)p1—C(═O)—, —(CHx)p1—C(═O)—O—, —(O—(CH2)p2—)p3—, —((CH2)p2—O—)p3—, —C(═S)—, —C(═S)—S—, —S—C(═S)—, —C(═S)—NH—, —S—C(═S)—S—, —S—, —SO—, —SO2—, —NR4—, —N(R4)—C(═O)—N(R8)—, —N(R4)—C(═O)O—, —N(R4)—C(═O)—, —C(═O)—N(R4)—, —C(═O)—N(R4)—C(═O)—, or —O—C(═O)—NR4—, wherein -alkylene-, -alkynylene-, -alkenylene-, -cycloalkylene-, -arylene-, -heteroarylene-, and -heterocyclylene- are optionally substituted;
• A3 is —CH2—, —CH2CH2—, or —CH2CH2CH2CH2—;
• R17 is selected from the group consisting of O, S, NR18, and CR5R6;
• R18 is selected from the group consisting of H, alkyl, alkynyl, alkenyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, and acyl, wherein alkyl, alkynyl, alkenyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, and acyl are optionally substituted;
• R4, R5, R6, and R8 are each independently H, or a substituted or unsubstituted:
• alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterocyclyl;
• R4a is a substituted or unsubstituted:
• alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterocyclyl;
• p1, p2, and p3 are each independently 0, or an integer from 1 to 100;
• and
• x is 2.