Probe of HIV peptide leads to drug-delivery clues

Scientists have known for years that HIV's "Tat" peptide can smuggle a variety of cargoes such as DNA fragments and small molecules into cells, making it useful in the design of drug-delivery systems. Now UCLA researchers have deepened their understanding of how the peptide slips into cells, and their findings could pave the way to a host of new delivery vehicles, the university reported.

Shedding more light on how the HIV peptide penetrates cells, the researchers show how the Tat interacts with the cell-surface receptors and the cell's actin cytoskeleton to gain entry in a variety of ways. With their insights, the researchers believe that new cell-penetrating peptides could be engineered, opening the door to targeted delivery of drugs to specific cells. Their work has been published in the journal Proceedings of the National Academy of Science.

"Prior to this, people didn't really know how it all worked, but we found that the HIV TAT peptide is really kind of like a Swiss Army Knife molecule, in that it can interact very strongly with membranes, as well as with the cytoskeletons of cells," said Gerard Wong, a professor at UCLA and lead author of the study, said, as quoted by the university. "The second part wasn't well appreciated by the field."

"We found that there are two channels of activity," Wong said. "Because of the peculiar sequence of HIV TAT, it's very good at being able to interact with membranes. Further, with the high-density packing of charged amino acids in the peptide, it can also interact very strongly with the cell's cytoskeleton, as well as its receptors."

- see UCLA's article

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