Engineering a noncarrier to a highly efficient carrier peptide for noncovalently delivering biologically active proteins into human cells.
Noncovalent protein delivery into cells via peptide carriers is an emerging concept. Only a handful of such peptides are known. To address various limitations associated with protein delivery for therapeutic purposes, a greater number of different delivery peptides would be required. No general method exists for creating such peptides. By combining a sequence of 16 lysine residues (K16) with the signal peptide (SP) sequence of Kaposi's fibroblast growth factor (K-FGF), we have synthesized a peptide (K16SP) that efficiently and noncovalently delivers functionally intact proteins (immunoglobulin G molecules, beta-galactosidase, and green fluorescent protein) into mammalian cells. The peptides K16 and SP each alone did not show any noncovalent protein-carrying capacity. K16SP appears to be nontoxic to cells and three to four times more efficient than a commercially available peptide reagent. Our approach offers proof-of-concept of a general strategy for creating a diverse array of peptide carriers for eventual therapeutic applications.
Mahlum
Eric
E
Department of Orthopedics, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Mandal
Deendayal
D
Halder
Chandralekha
C
Maran
Avudaiappan
A
Yaszemski
Michael J
MJ
Jenkins
Robert B
RB
Bolander
Mark E
ME
Sarkar
Gobinda
G
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods*; D051519:Fibroblast Growth Factor 4 / Q000737:chemistry* / Q000378:metabolism*; D006041:Goats; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D008239:Lysine; D015202:Protein Engineering / Q000379:methods*; D021382:Protein Sorting Signals; D021381:Protein Transport; D014162:Transfection
D002352:Carrier Proteins; C496445:FGF4 protein, human; D051519:Fibroblast Growth Factor 4; D007074:Immunoglobulin G; D021382:Protein Sorting Signals; D008239:Lysine