Recently, the antibiotic resistance of bacteria caused by the inappropriate use of antibiotics becomes a severe problem. In fact, the rate at which bacteria exhibit resistance to new antibiotics is faster than the rate at which the analogues of the new antibiotics are developed. The condition preceding the antibiotic resistance of bacteria is that bacteria have tolerance to antibiotics. The bacteria showing tolerance to antibiotics stop their growth in the presence of a general concentration of antibiotics, but do not ultimately die.
Tolerance occurs since the activity of bacterial autolytic enzymes, such as autolysin, does not occur when antibiotics inhibit cell wall synthetase. As a result of the above fact, penicillin activates endogenous hydrolytic enzymes to kill bacteria, but the bacteria inhibit the activity of the enzymes such that they survive even in antibiotics treatment. Actually, since all bacteria showing antibiotic resistance are known as having tolerance as well, there is a need for the development of new antibiotics capable of killing bacteria with antibiotic resistance.
Thus, many studies to develop new antibiotics against bacteria are being conducted, and among them, the development of peptides showing antibacterial activity is predominant. In the natural system, bacteria synthesize peptides or small organic molecules to be able to kill adjacent bacteria, and such bacteriocins are structurally classified into the following three categories: (1) lantibiotics, (2) non-lantibiotics, and (3) antibiotics secreted by a signal peptide.
Animals, including insects, also produce naturally occurring peptides. Such peptide antibiotics are structurally classified into the following three categories: (1) cysteine-rich sheet peptides, (2) cysteine-rich helical amphiphilic molecules, (3) proline-rich peptides. These antibacterial peptides are known to play an important role in a host defense and a native immune system.
Such antibacterial peptides have various structures depending on their amino acid sequence, and among such structures, the one that is most frequently present is an amphiphilic alpha-helical structure with no cysteine residues, such as cecropin that is an antibacterial peptide found in insects. Many studies on the antibacterial activity of amphiphilic peptides were conducted, and the amphiphilic peptides reported till now include magainin 2 (MA), cecropin A (CA), melittin (ME) and the like.
USPTO Backgrounds
USPTO Backgrounds