Haynie S L, Crum G A, Doele B A
Central Research & Development, E. I. DuPont de Nemours & Co., Wilmington, DE 19880-0328, USA.
Antimicrob Agents Chemother. 1995 Feb;39(2):301-7. doi: 10.1128/AAC.39.2.301.
A series of polymer-bound antimicrobial peptides was prepared, and the peptides were tested for their antimicrobial activities. The immobilized peptides were prepared by a strategy that used solid-phase peptide synthesis that linked the carboxy-terminal amino acid with an ethylenediamine-modified polyamide resin (PepsynK). The acid-stable, permanent amide bond between the support and the nascent peptide renders the peptide resistant to cleavage from the support during the final acid-catalyzed deprotection step in the synthesis. Select immobilized peptides containing amino acid sequences that ranged from the naturally occurring magainin to simpler synthetic sequences with idealized secondary structures were excellent antimicrobial agents against several organisms. The immobilized peptides typically reduced the number of viable cells by > or = 5 log units. We show that the reduction in cell numbers cannot be explained by the action of a soluble component. We observed no leached or hydrolyzed peptide from the resin, nor did we observe any antimicrobial activity in soluble extracts from the immobilized peptide. The immobilized peptides were washed and reused for repeated microbial contact and killing. These results suggest that the surface actions by magainins and structurally related antimicrobial peptides are sufficient for their lethal activities.
制备了一系列聚合物结合的抗菌肽，并对这些肽的抗菌活性进行了测试。固定化肽是通过一种策略制备的，该策略采用固相肽合成法，将羧基末端氨基酸与乙二胺修饰的聚酰胺树脂（PepsynK）相连。载体与新生肽之间形成的耐酸永久性酰胺键，使得肽在合成的最后酸催化脱保护步骤中不会从载体上裂解下来。选择含有从天然存在的蛙皮素到具有理想化二级结构的更简单合成序列的氨基酸序列的固定化肽，对几种生物体来说都是优秀的抗菌剂。固定化肽通常能使活细胞数量减少≥5个对数单位。我们表明，细胞数量的减少不能用可溶性成分的作用来解释。我们没有观察到树脂中有浸出或水解的肽，也没有在固定化肽的可溶性提取物中观察到任何抗菌活性。固定化肽经过洗涤后可重复用于与微生物的反复接触和杀灭。这些结果表明，蛙皮素和结构相关的抗菌肽的表面作用足以产生其致死活性。
