Design, Synthesis, and Characterization of a Cationic Peptide That Binds to Nucleic Acids and Permeabilizes Bilayers
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- 作者：Tara B. Wyman ; Franç ; ois Nicol ; Olivier Zelphati ; P. V. Scaria ; Christian Plank ; and Francis C. Szoka ; Jr.
- 刊名：Biochemistry
- 出版年：1997
- 出版时间：March 11, 1997
- 年：1997
- 卷：36
- 期：10
- 页码：3008 - 3017
- 全文大小：325K
- 年卷期：v.36,no.10(March 11, 1997)
- ISSN：1520-4995
文摘
We have designed a cationic amphipathic peptide, KALA(WEAKLAKALAKALAKHLAKALAKALKACEA), that binds to DNA, destabilizes membranes, andmediates DNA transfection.KALA undergoes a pH-dependent random coil to amphipathic
-helical conformational change as thepH is increased from 5.0 to 7.5. One face displays hydrophobicleucine residues, and the opposite facedisplays hydrophilic lysine residues. KALA-mediated release ofentrapped aqueous contents from neutraland negatively charged liposomes increases with increasing helicalcontent. KALA binds to oligonucleotides or plasmid DNA and retards their migration in gelelectrophoresis. It displaces 50% of ethidiumbromide from DNA at a charge ratio (+/-) of 0.9/1. In culturedcells, KALA assists oligonucleotidenuclear delivery when complexes are prepared at a 10/1 (+/-) chargeratio. KALA/DNA (10/1) (+/-)complexes mediate transfection of a variety of cell lines. TheKALA sequence provides a starting pointfor a family of peptides that incorporate other functions to improveDNA delivery systems.
-helical conformational change as thepH is increased from 5.0 to 7.5. One face displays hydrophobicleucine residues, and the opposite facedisplays hydrophilic lysine residues. KALA-mediated release ofentrapped aqueous contents from neutraland negatively charged liposomes increases with increasing helicalcontent. KALA binds to oligonucleotides or plasmid DNA and retards their migration in gelelectrophoresis. It displaces 50% of ethidiumbromide from DNA at a charge ratio (+/-) of 0.9/1. In culturedcells, KALA assists oligonucleotidenuclear delivery when complexes are prepared at a 10/1 (+/-) chargeratio. KALA/DNA (10/1) (+/-)complexes mediate transfection of a variety of cell lines. TheKALA sequence provides a starting pointfor a family of peptides that incorporate other functions to improveDNA delivery systems.