TAT-GluA2 3Y peptide

• Handling and Storage of Synthetic Peptides
• Material Safety Data Sheets (MSDS)

Batch to batch variation of the purity

The TAT-GluA2 3Y peptide is a synthetic interference peptide composed of 9 amino acids (YKEGYNVYG) linked to an HIV-1 Tat peptide (YGRKKRRQRRR) for blood-brain barrier penetration and cellular uptake. This peptide selectively disrupts the endocytosis of GluA2-containing AMPA receptors (AMPARs) by inhibiting the interaction between the GluA2 subunit and the clathrin-adaptor protein Brag2, which activates Arf6 to initiate receptor internalization. By blocking AMPAR endocytosis, TAT-GluA2 3Y prevents long-term depression (LTD) at glutamatergic synapses, a form of synaptic plasticity implicated in neural adaptations.

Studies demonstrate that TAT-GluA2 3Y administration attenuates neurochemical and behavioral responses associated with repeated psychostimulant exposure. Systemic delivery of the peptide during the induction phase of sensitization reduces dopamine efflux in the nucleus accumbens (NAcc) and blocks the maintenance of sensitized locomotor activity. Furthermore, intracerebral microinjection into the ventral tegmental area (VTA), but not the NAcc, inhibits the expression of sensitization, suggesting region-specific modulation of synaptic plasticity. These findings highlight the role of GluA2-containing AMPAR trafficking in neuroadaptations linked to associative learning processes.

• Choi FY, Ahn S, Wang YT, Phillips AG. Interference with AMPA receptor endocytosis: effects on behavioural and neurochemical correlates of amphetamine sensitization in male rats. J Psychiatry Neurosci. 2014 May;39(3):189-99. doi: 10.1503/jpn.120257. PMID: 24290077; PMCID: PMC3997604.

Trifluoroacetic acid (TFA) has a significant impact on peptides due to its role in the peptide synthesis process.

TFA is essential for the protonation of peptides that lack basic amino acids such as Arginine (Arg), Histidine (His), and Lysine (Lys), or ones that have blocked N-termini. As a result, peptides often contain TFA salts in the final product.

TFA residues, when present in custom peptides, can cause unpredictable fluctuations in experimental data. At a nanomolar (nM) level, TFA can influence cell experiments, hindering cell growth at low concentrations (as low as 10 nM) and promoting it at higher doses (0.5–7.0 mM). It can also serve as an allosteric regulator on the GlyR of glycine receptors, thereby increasing receptor activity at lower glycine concentrations.

In an in vivo setting, TFA can trifluoroacetylate amino groups in proteins and phospholipids, inducing potentially unwanted antibody responses. Moreover, TFA can impact structure studies as it affects spectrum absorption.