Synthesis And Activity Research Of Transdermal Peptides

Transdermal drug delivery system (Transdermal therapeutic system, the TTS or Transdermal delivery, TDS), which is the drug (or close to constant speed) through the skin layers into the systemic circulation at a constant speed, resulting in local or systemic therapeutic and effective new delivery method. Compared to traditional oral and subcutaneous intravenous, transdermal drug delivery had convenience, sustainability and controllability advantages, etc.TD1is a11amino acids peptide (ACSSSPSKHCG), could promote the insulin molecule and macromolecular protein drugs into animal blood circulation through a simple mixing smear way and play its therapeutic effect.This paper designed and synthesized a series of TD1analogues with peptide solid phase synthesis technology,Using transdermal peptides and antimicrobial peptides of molecular structural features to change the amino acid residues in transdermal peptide composition for transdermal peptides TD1which has been to reported. We use lysine or arginine scan to increase the number of cation and change the location to improve the transdermal effect. This paper use Wang-resin for solid phase carrier, Fmoc protecting group for the N-terminal amino acid, HBTU-HOBt as the condensing agent, the TFA for resin removal of reagents.We have been successfully synthesized11designed peptide sequences. Purificating with molecular sieve for crude peptide and characterizing by reversed-phase high performance liquid chromatography and mass spectrometry confirmed that in accord with the theoretical value. This paper also analysised secondary structures of synthetic peptide by Circular dichroism.This paper did the antibacterial experiments of sequence of the synthetic peptides.TDl’s capable of carrying large proteins through the cell membrane, and the antimicrobial peptide also have the same combination of cell surface and undermine its integrity and produce perforation in order to cause the material overflow the cytoplasm and death. According to the peptide’s design ideas, combined with the antimicrobial peptides antibacterial principle, we used the checkerboard microdilution96-well plates to measure the TD1analogues minimum inhibitory concentration and calculate the inhibition rate. And according with design idea, we discussed the relationship between structure and activity. The activity results show that the contrast to the positive control (antimicrobial peptides Arg-7), synthetic drugs inhibitory effect of E. coli up to66.33%inhibition of Staphylococcus aureus up to a maximum of129.05%and the experiments show TDL2, TDL3medication reduce the blood glucose concentration to the initial level of72.77%and50.91%after8h in vitro on type I diabetic rats.Depending on the size of the inhibition rate, we compared the similar sequence of the antibacterial effect of the TD1. Compared the role of TS and TD1, we can know that the11amino acid residues is the smallest residues of this sequence, and in its peptide acids, verycomparison, charge, Lys and Arg can better improve its antibacterial effect, it is related to type of the amino acids and substitution position. Further increase in the number of Lys to change its polarity to increase its ability to dissolve and positive charge, but its inhibitory effect is not obvious, mybe it is the binding capacity of the drug with the cell membrane charge to reach saturation or about hydrophobic active center. The circular dichroism results showed that the synthetic peptide did not appear characteristic absorption peak.It is mainly related to the number and types of amino acids residues. Map show their secondary structure were random coil.