Synthesis and antimicrobial activity of the symmetric dimeric form of temporin a based on 3-N,N-di(3-aminopropyl)amino propanoic acid as the branching unit

Dimeric derivative of antimicrobial peptide amide Temporin A (TA) was synth esized by using a new branching unit 3-N,N-di(3-aminopropyl)amino propanoic acid (DAPPA), which allows building of the parallelly symmetric alpha -hel ical structures. Antimicrobial effect of the original peptide amide, its mo nomeric carboxy (TAc) and novel dimeric (TAd) analogues were tested against Staphylococus aureus (Gram-positive) and Escherichia coli (Gram-negative). Both TA and TAd completely inhibited the growth of S, aureus at the concen trations of 5 and 10 muM, respectively, whereas TAc did not show any inhibi tory activity. The activities of TAc, TA and TAd correlate directly with th e net charges of the molecules, + 1, + 2 and + 4, respectively. Interesting ly, TAd displayed antibacterial effect against E, coli at a concentration o f 10 muM, where as monomeric TA did not show any activity at concentration as high as 20 muM The results indicate that the novel structural modificati on improves the antibacterial properties of Temporin A especially towards G ram-negative bacteria. (C) 2001 Elsevier Science Ltd. All rights reserved.