ABSTRACT
To find anti-hypertensive lead drug, angiotensin converting enzyme (ACE) inhibitory peptides were synthesized and their effects on inhibiting ACE activity were investigated. ACE inhibitory peptides were synthesized via Fmoc solid-phase synthesis, isolated and purified through reversed phase high-performance liquid chromatography (RP-HPLC), and identified by mass spectrometry. A RP-HPLC analysis method was used to test ACE inhibitory activity in vitro of these ACE inhibitory peptides. Six octapeptides were successfully synthesized, and the analytical results of mass spectrum were consistent with their theoretically calculated data. Among these synthetic octapeptides, the anti-SARS (severe acute respiratory syndromes) octapeptide had the most obvious ACE inhibitory activity with an IC50 value of 3.4 x 10(-5) mol x L(-1). So octapeptide AVLQSGFR-OH (anti-SARS peptide) was found to be the strongest candidate for potential development as an anti-hypertensive drug and had the implication of further study.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Chemistry , Pharmacology , Antihypertensive Agents , Chemistry , Pharmacology , Chromatography, High Pressure Liquid , Methods , Mass Spectrometry , Molecular Structure , Oligopeptides , Chemistry , Pharmacology , Peptidyl-Dipeptidase A , Solid-Phase Synthesis TechniquesABSTRACT
Biomacromolecules play an important role in the treatment of many diseases, but as a result of cell membrane serving as the natural barriers, only the small molecular compounds whose molecular weights are smaller than 600 Da can get through cell membrane and enter the cell. In recent years, some short peptides (the length less than 30 amino acids) are found to have the cell-penetrating function, called cell-penetrating peptides (CPPs). They are able to effectively translocate segments of protein, polypeptides, nucleic acid into the cells of many mammal animals with many methods. They have high transduction efficiency and will not lead to cell damage. So, the discovery of CPPs has a very good applicable prospect in such research fields as cell-biology, gene-therapy, drug transduction in vivo, evaluation of clinical medicine and medical immunology. This paper reviews the types and characteristics of CPPs, internalization mechanisms, applications, and their existing problems.