发明授权
- 专利标题: Antimicrobial magainin modified peptides
- 专利标题(中): 抗菌马卡宁修饰肽
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申请号: US280363申请日: 1988-12-06
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公开(公告)号: US5221732A公开(公告)日: 1993-06-22
- 发明人: Hao-Chia Chen , Judith H. Brown , John L. Morell , Charng-Ming Huang
- 申请人: Hao-Chia Chen , Judith H. Brown , John L. Morell , Charng-Ming Huang
- 申请人地址: DC Washington
- 专利权人: The United States of America as represented by the Department of Health and Human Services
- 当前专利权人: The United States of America as represented by the Department of Health and Human Services
- 当前专利权人地址: DC Washington
- 主分类号: A61K38/00
- IPC分类号: A61K38/00 ; C07K14/46
摘要:
Peptides which exhibit improved broad spectrum antimicrobial activity are designed and synthesized based on the peptide sequences of magainin or PGS peptides. The modified peptide analogues are synthesized by replacing low helical potential amino acid residues with high helical potential residues and modifying the two termini in order to enhance the amphiphilic structures as well as to prolong antimicrobial activity by lowering their susceptibility to protease degradation. For example, low propensity residues within a strategic region of magainin II, e.g. Ser.sup.8, Gly.sup.13 and Gly.sup.18 are modified with Ala which is known to have high propensity. Amidation of Ser.sup.23, and acylation of Gly.sup.1 with acetyl or beta-alanyl and substitution of Gly.sup.1 with beta-alanine are carried out in order to lower the susceptibility to exopeptidase action. A D-Ala modification for disrupting a stretch of the helical structure is also prepared so as to demonstrate the importance of an amphiphilic helical structure for antimicrobial activity. The modified peptide analogues exhibit an increase of up to two orders of magnitude in antimicrobial activity and, in the most favorable case, no appreciable increase in hemolytic activity over magainin 1.