pHLIP（pH low insertion peptide）

pHLIP（pH low insertion peptide）

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

Batch to batch variation of the purity

H-ACEQNPIYWARYADWLFTTPLLLLDLALLVDADEGT-OH

H-Ala-Cys-Glu-Gln-Asn-Pro-Ile-Tyr-Trp-Ala-Arg-Tyr-Ala-Asp-Trp-Leu-Phe-Thr-Thr-Pro-Leu-Leu-Leu-Leu-Asp-Leu-Ala-Leu-Leu-Val-Asp-Ala-Asp-Glu-Gly-Thr-OH

36

95.39%

C₁₉₁H₂₈₅N₄₃O₅₆S

4111.6

Synthetic

Powder

The peptide pHLIP (pH (Low) Insertion Peptide) is a unique molecule with important characteristics. It is designed to target acidic environments. Under low pH conditions (usually associated with diseased tissues such as tumors), it can insert into cell membranes, making it a promising tool for targeted drug delivery and imaging. pHLIP can act as a carrier to specifically deliver therapeutic agents or imaging probes to acidic regions, enhancing the specificity and efficacy of treatments while reducing side effects on healthy tissues. Its mechanism of action is based on pH-dependent membrane-associated folding. Under low pH conditions commonly found in diseased tissues such as tumors, it folds into a helical conformation that releases free energy and then inserts into cell membranes, thereby selectively targeting cancerous tissues with an extracellular pH of about 6.0 - 6.8 while avoiding retention in healthy tissues with a pH of about 7.2 - 7.4.

Normally, this peptide will be delivered in lyophilized form and should be stored in a freezer at or below -20 °C. For more details, please refer to the manual: Handling and Storage of Synthetic Peptides

• Tapmeier TT, Moshnikova A, Beech J, Allen D, Kinchesh P, Smart S, Harris A, McIntyre A, Engelman DM, Andreev OA, Reshetnyak YK, Muschel RJ. The pH low insertion peptide pHLIP Variant 3 as a novel marker of acidic malignant lesions. Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):9710-5. doi: 10.1073/pnas.1509488112. Epub 2015 Jul 20. PMID: 26195776; PMCID: PMC4534280.
• Wei Y, Liao R, Mahmood AA, Xu H, Zhou Q. pH-responsive pHLIP (pH low insertion peptide) nanoclusters of superparamagnetic iron oxide nanoparticles as a tumor-selective MRI contrast agent. Acta Biomater. 2017 Jun;55:194-203. doi: 10.1016/j.actbio.2017.03.046. Epub 2017 Mar 29. PMID: 28363789.

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.