Brittany deRonde/Sandbox 1

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	== '''Cell Penetrating Peptides''' ==		== '''Cell Penetrating Peptides''' ==
-	'''Cell penetrating peptides (CPPs)''' are proteins with the ability to cross cellular membranes and facilitate the uptake of various cargo, such as small molecules, siRNA, and small DNA fragments.<ref>Futaki ''et al. J. Biol. Chem.'' '''2001'''. 276, 5836-5840.</ref> Such cargo can be associated via covalent or non-covalent interactions. Tat is considered a CPP because it contains a protein transduction domain (PTD). PTDs are cation-rich sequences of 10-30 residues found in proteins, usually containing several Lysine and/or Arginine residues.<ref>Wender ''et al. Adv. Drug Deliv. Rev.'' '''2008'''. 60, 452-472.</ref>	+	'''Cell penetrating peptides (CPPs)''' are proteins with the ability to cross cellular membranes and facilitate the uptake of various cargo, such as small molecules, siRNA, and small DNA fragments.<ref>Futaki ''et al. J. Biol. Chem.'' '''2001'''. 276, 5836-5840.</ref> Such cargo can be associated via covalent or non-covalent interactions. Tat is considered a CPP because it contains a protein transduction domain (PTD). PTDs are cation-rich sequences of 10-30 residues, usually containing several Lysine and/or Arginine residues.<ref>Wender ''et al. Adv. Drug Deliv. Rev.'' '''2008'''. 60, 452-472.</ref>
	[[Image:Arginine1.jpg]] [[Image:Lysine1.jpg]]		[[Image:Arginine1.jpg]] [[Image:Lysine1.jpg]]
-	These sequences enable favorable interactions with cellular membranes that help them to enter cells. The PTD sequence in Tat is YGRKKRRQRRR (amino acid <scene name='Brittany_deRonde/Sandbox_1/Hiv_tat/3'>residues 47-57</scene>), which is Arginine-rich. This 11 amino-acid sequence is now referred to as the TAT peptide, and has be shown to have improved cellular uptake compared to Tat. The mechanism of uptake is still highly debated in the literature.	+	These sequences improve interactions between CPPs and cellular membranes and can help them enter cells. The PTD sequence in Tat is YGRKKRRQRRR (amino acid <scene name='Brittany_deRonde/Sandbox_1/Hiv_tat/3'>residues 47-57</scene>), which is Arginine-rich. This 11 amino-acid sequence is now referred to as the TAT peptide, and has be shown to have improved cellular uptake compared to Tat.
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		+	Since the discovery of HIV Tat, other natural CPPs have been discovered including, penetratin from Drosophila antennapedia protein, sweet arrow peptide (SAP), HIV-1 Rev, flock house virus (FHV) coat, brome mosaic virus (BMV) Gag, human T-cell lymphotrophic virus (HTLV)-II Rex, and the nuclear localization signal (NLS) from nucleoplasmin. <ref>Futaki ''et al. J. Biol. Chem.'' '''2001'''. 276, 5836-5840.<ref/>
	== '''Tat-mediated Transduction''' ==		== '''Tat-mediated Transduction''' ==

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Revision as of 15:31, 16 December 2011

One of the CBI Molecules being studied in the University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground.

Introduction

HIV Tat, or simply Tat, is a human immunodeficiency virus (HIV) gene that regulates transcription of HIV dsRNA.^[1] Tat, which stands for trans-activator of transcription, contains 86 amino acid residues in its sequence.^[2][3]

spinqualitylabelsall models Insert caption here Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

It is released by HIV infected cells in order to enhance replication of the virus.^[4][5] Nanomolar concentrations of Tat have been reported in the blood of HIV-1 infected people.^[6] When the protein enters non-infected cells, the transcription efficiency increases. It is estimated that transcription levels are 10 to 100 fold higher during the transcription elongation stage when compared to normal basal transcription.^[7] Green and Lowenstein, and Frankel and Pabo independently published studies in 1988 that demonstrated that Tat had the ability to cross cellular membranes and initiate transcription of HIV dsRNA.^[8][9] These were the first known reports of a cell penetrating peptide (CPP).

Cell Penetrating Peptides

Cell penetrating peptides (CPPs) are proteins with the ability to cross cellular membranes and facilitate the uptake of various cargo, such as small molecules, siRNA, and small DNA fragments.^[10] Such cargo can be associated via covalent or non-covalent interactions. Tat is considered a CPP because it contains a protein transduction domain (PTD). PTDs are cation-rich sequences of 10-30 residues, usually containing several Lysine and/or Arginine residues.^[11]

These sequences improve interactions between CPPs and cellular membranes and can help them enter cells. The PTD sequence in Tat is YGRKKRRQRRR (amino acid ), which is Arginine-rich. This 11 amino-acid sequence is now referred to as the TAT peptide, and has be shown to have improved cellular uptake compared to Tat.

Since the discovery of HIV Tat, other natural CPPs have been discovered including, penetratin from Drosophila antennapedia protein, sweet arrow peptide (SAP), HIV-1 Rev, flock house virus (FHV) coat, brome mosaic virus (BMV) Gag, human T-cell lymphotrophic virus (HTLV)-II Rex, and the nuclear localization signal (NLS) from nucleoplasmin. ^[12]