Part:BBa_K5384003

Asp-Pro (acid sensitive site)

ASP-PRO acid-sensitive sites are regions of aspartic acid (ASP) and proline (PRO) in a specific protein or peptide sequence that are sensitive to acidic environments. Under acidic conditions, specific structural changes or chemical reactions may occur at this site. The presence of such acid-sensitive sites may affect the overall structure and stability of the protein. It can be used to design acid-sensitive drug delivery systems. It remains stable in a normal physiological environment, but changes in a specific acidic pathological environment (such as tumor tissue, lysosomes, etc.), resulting in the release of the drug. In some biological processes, it may be involved in the folding, degradation, or functional regulation of proteins.

Usage and Biology

We introduce Asp-Pro acid-sensitive sites between the fusion parter and antimicrobial,using acid to cleave fusion peptide. Acid sensitive site, which is distributed between vg and vg and other elements,resulting in separate vg, in acidic environment. Aspartic acid and glutamic acid are both acidic amino acids, and the pKa is about 3.9. The peptide pHLIP is a 36-peptide containing aspartic acid (table 1). The slightly acidic environment on the surface of cancer cells can trigger pHLIP to alter its structure and insert into the cell membrane of cancer cells. pHLIP has three conformations in solution, non-structural monomers (state I.), membrane-bound non-structural monomers (state II), and membrane-inserted monomers (state III.) .The transition from state II. to III. is achieved by the carboxyl-based protonation of aspartic acid under acidic conditions to form α-helix. The transmembrane part of pHLIP contains two aspartic acid residues, which are deprotonated by carboxyl groups at physiological pH, and the negatively charged residues increase the hydrophilicity of the polypeptide, prevent it from entering the hydrophobic region of the lipid bilayer of the cell membrane, and play a role in anchoring the polypeptide to the surface of the cell membrane. In the acidic environment, pHLIP transforms into a α-helix structure due to the carboxyl-protonation of aspartic acid.[1，2，3]

Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  COMPATIBLE WITH RFC[25]
• 1000
  COMPATIBLE WITH RFC[1000]

Application

In order to facilitate the separation of the target peptide from the fusion partner, the acid-sensitive aspartyl-proline (Asp-Pro) sites are added, and the expression plasmid pPIC9K-3Vg-3his. It remains stable in a normal physiological environment, but changes in a specific acidic pathological environment (such as tumor tissue, lysosomes, etc.), resulting in the release of the drug. In some biological processes, it may be involved in the folding, degradation, or functional regulation of proteins.

References

[1] Protein Science ( IF 4.5 ) Pub Date : 2024-02-21 ,Noa Yeshaya 1 , Prashant Kumar Gupta 2 , Orly Dym 3 , David Morgenstern 4 , Dan Thomas Major 2 , Deborah Fass 1

[2] ZHAO Huan-le, LIANG Ju, WU Wen-lan, LI Jun-bo. Mechanism and application of acid-sensitive peptides in drug delivery. Acta Pharmaceutica Sinica, 2019, 54(3): 440-447.

[3] Xu Xuejiao. Construction of prokaryotic and eukaryotic secretion expression systems of cationic antimicrobial peptides[D].Anhui University,2015.