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The natural antimicrobial cationic peptide protegrin-1 displays a broad spectrum of antimicrobial activity and rapidly kills pathogens by interacting with their cell membrane. We investigated the structure–activity relation-ships of three protegrin-1 analogues: IB-367 (RGGLCYCRGRFCVCVGR-NH2), BM-1 (RGLCYCRGRFCVCVG-NH2) and BM-2 (RGLCYRPRFV CVG-NH2). Our antimicrobial and antifungal activity studies of these peptides showed that BM-1 was much more active than IB-367 against Gram-positive bacteria and fungi, whereas BM-2 was inactive. . | ễFEBS Journal Antimicrobial and conformational studies of the active and inactive analogues of the protegrin-1 peptide Sylwia Rodziewicz-Motowidto1 Beata Mickiewicz1 Katarzyna Greber2 Emilia Sikorska1 bukasz Szultka2 Elzbieta Kamysz1 and Wojciech Kamysz2 1 Faculty of Chemistry University of Gdansk Poland 2 Faculty of Pharmacy MedicalUniversity of Gdansk Poland Keywords antimicrobialpeptides IB-367 NMR protegrin-1 analogues three-dimensional structure Correspondence S. Rodziewicz-Motowidto Faculty of Chemistry University of Gdansk Sobieskiego 18 80-952 Gdansk Poland Fax 48 58 523 54 72 Tel 48 58 52 35 430 E-mail sylwia@chem.univ.gda.pl Received 11 August 2009 revised 6 November 2009 accepted 9 December 2009 doi 10.1111 j.1742-4658.2009.07544.x The natural antimicrobial cationic peptide protegrin-1 displays a broad spectrum of antimicrobial activity and rapidly kills pathogens by interacting with their cell membrane. We investigated the structure-activity relationships of three protegrin-1 analogues IB-367 RGGLCYCRGRFCVCVGR-NH2 BM-1 RGLCYCRGRFCVCVG-NH2 and BM-2 RGLCYRPRFV CVG-NH2 . Our antimicrobial and antifungal activity studies of these peptides showed that BM-1 was much more active than IB-367 against Gram-positive bacteria and fungi whereas BM-2 was inactive. The BM-1 peptide showed fourfold reduced haemolysis relative to IB-367 an additional advantage of this peptide. In addition BM-1 was about 15 cheaper than IB-367 to synthesize. The absence of two cysteine residues in the BM-2 sequence could be the main reason for its unstable conformation and antimicrobial inactivity. The solution structures of these peptides were determined in dimethyl sulphoxide using two-dimensional NMR and restrained molecular dynamics calculations. IB-367 and BM-1 formed short antiparallel b-hairpin structures connected by a type II b-turn. The shorter inactive BM-2 analogue exhibited major and minor conformations predominantly unordered in the NMR spectra and was much more flexible. .
