Peptides whose uptake in cells is controllable

Abstract

Disclosed herein, in certain embodiments, is a selective transport molecule with increased in vivo circulation. In some embodiments, a selective transport molecule disclosed herein has the formula (A-X-B-C)-M, wherein C is a cargo moiety; A is a peptide with a sequence comprising 5 to 9 consecutive acidic amino acids, wherein the amino acids are selected from: aspartates and glutamates; B is a peptide with a sequence comprising 5 to 20 consecutive basic amino acids; X is a linker; and M is a macromolecular carrier.

1 .- 76 . (canceled) 
     
     
         77 . A molecule comprising a structure A-X-B-C attached to a reactive group,
 wherein   A is a peptide with a sequence comprising a series of 5 to 9 acidic amino acids, wherein the amino acids are selected from: aspartates and glutamates;   B is a peptide with a sequence comprising a series of 5 to 20 basic amino acids;   X is a cleavable linker; and   C is a therapeutic cargo; and   wherein the reactive group is maleimide.   
     
     
         78 . The molecule of  claim 77 , wherein the maleimide is attached to A. 
     
     
         79 . The molecule of  claim 77 , wherein the maleimide is attached to the N-terminus of A. 
     
     
         80 . The molecule of  claim 77 , wherein the maleimide is attached to the N-terminus of A through a linker. 
     
     
         81 . The molecule of  claim 80 , wherein the linker comprises a heterobifunctional linker. 
     
     
         82 . The molecule of  claim 80 , wherein the linker further comprises a hydrophilic PEG chain. 
     
     
         83 . The molecule of  claim 80 , wherein the linker further comprises a hydrophobic carbon chain. 
     
     
         84 . The molecule of  claim 77 , wherein A has a sequence comprising a series of 5 to 9 glutamates. 
     
     
         85 . The molecule of  claim 77 , wherein A has a sequence comprising a series of 9 glutamates. 
     
     
         86 . The molecule of  claim 77 , wherein A has a sequence comprising a series of 5 glutamates. 
     
     
         87 . The molecule of  claim 77 , wherein B has a sequence comprising a series of 5 to 12 arginines. 
     
     
         88 . The molecule of  claim 77 , wherein B has a sequence comprising a series of 9 arginines. 
     
     
         89 . The molecule of  claim 77 , wherein B has a sequence comprising a series of 8 arginines. 
     
     
         90 . The molecule of  claim 77 , wherein A and B comprise D-amino acids. 
     
     
         91 . The molecule of  claim 77 , wherein X is selected from: PLGLAG, PLGLAx wherein X is any amino acid, PLG-C(me)-AG, ESPAYYTA, and RLQLKL, AND RLQLK(AC). 
     
     
         92 . The molecule of  claim 77 , wherein C is selected from: a chemotherapeutic agent, a radiation sensitizer, an agent that modulates apoptosis, an agent that modulates the cell cycle, an agent that modulates a signaling cascade, or a combination thereof. 
     
     
         93 . The molecule of  claim 77 , wherein the maleimide interacts with an albumin in vivo. 
     
     
         94 . The molecule of  claim 93 , wherein the albumin is human albumin. 
     
     
         95 . The molecule of  claim 77 , wherein the molecule is formulated as a pharmaceutical composition for administration into a subject.