Study On The Stability Of Deuterohemin Short Peptide In Vitro

Polypeptide drugs have played a very important role in many areas intoday’s pharmaceutical market.They often representing the smallestfunctional part of a protein, and offer greater efficacy, selectivity andspecificity than small organic molecules. Another advantage is that thedegradation products of peptides are amino acids, thus minimizing therisks of systemic toxicity. But they generally have low stability inplasma, are sensitive to proteases and can be cleared from the circulationin a few minutes.Therefore, various chemical strategies have beendeveloped to try and overcome the limitations of peptides to increasetheir in vivo plasma residence time.Our laboratory designed a new kind of peroxides mimics Deuterohaemin-βAla-His-Thr-Val-Glu-Lys(DhHP-6) which has the ability of catalysisdecomposing peroxide and promotes the proliferation of thecell,Antioxidant，Anti-aging，increasing the average life of C.elegansby about20%in vitro..However, fewer studies on stability.According to the preliminary work,we synthesized DeuteroheminShort Peptides by solid-phase peptide synthesis(SPPS) method.Study on thestability of Deuterohemin Short Peptides in plasma,simulated gastricfluid,simulated intestinal fluid by HPLC analysis,MS detection.Experimental results show that the plasma in vitro, the Deuteroheminpeptide compared to the corresponding linear peptide, the stabilitygreatly improved, half-life was obviously extended; in the simulatedgastric fluid,simulated intestinal fluid which the peptide drugs can be easily degradation, the Deuterohemin peptides compound also has a verygood performance, compared with the corresponding linear peptide, thestability greatly improved.That indicating the Deuterohemin group caneffectively improve the stability and extend the half-life of thepeptide, has a protective effect on peptide sequence. This experimentwill help design and application of research containing porphyrin ringof metal porphyrin peptides and proteins, in order to improve thestability of peptide drugs offer a new way, with potential clinicalsignificance.