The Outcomes of Decorated Prolines in the Discovery of Antimicrobial Peptides from Temporin-L

被引:26
作者
Buommino, Elisabetta [1 ]
Carotenuto, Alfonso [1 ]
Antignano, Ignazio [1 ]
Bellavita, Rosa [1 ]
Casciaro, Bruno [2 ,6 ]
Loffredo, Maria Rosa [2 ]
Merlino, Francesco [1 ]
Novellino, Ettore [1 ]
Mangoni, Maria Luisa [2 ]
Nocera, Francesca Paola [5 ]
Brancaccio, Diego [1 ]
Punzi, Pasqualina [3 ]
Roversi, Daniela [3 ]
Ingenito, Raffaele [3 ]
Bianchi, Elisabetta [3 ]
Grieco, Paolo [1 ,4 ]
机构
[1] Univ Naples Federico II, Dept Pharm, I-80131 Naples, Italy
[2] Sapienza Univ Rome, Lab Pasteur Inst Italia Fdn Cenci Bolognetti, Dept Biochem Sci, I-00185 Rome, Italy
[3] IRBM SpA, Peptide Chem Unit, Via Pontina Km 30600, I-00071 Pomezia, Italy
[4] Univ Naples Federico II, Ctr Interuniv Ric Peptidi Bioattivi CIRPEB, Naples, Italy
[5] Univ Naples Federico II, Dept Vet Med & Anim Prod, I-80137 Naples, Italy
[6] Ist Italiano Tecnol, Ctr Life Nano Sci, I-00161 Rome, Italy
关键词
antimicrobial peptides; biological activity; conformational studies; synthesis; temporin L analogues; HOST-DEFENSE PEPTIDES; RESISTANT STAPHYLOCOCCUS-AUREUS; SECONDARY STRUCTURE; PREDICTION; MECHANISM; DESIGN; SYSTEM; PHASE;
D O I
10.1002/cmdc.201900221
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Previously, we identified a potent antimicrobial analogue of temporin L (TL), [Pro(3)]TL, in which glutamine at position 3 was substituted with proline. In this study, a series of analogues in which position 3 is substituted with non-natural proline derivatives, was investigated for correlations between the conformational properties of the compounds and their antibacterial, cytotoxic, and hemolytic activities. Non-natural proline analogues with substituents at position 4 of the pyrrolidine ring were considered. Structure-activity relationship (SAR) studies of these analogues were performed by means of antimicrobial and cytotoxicity assays along with circular dichroism (CD) and NMR spectroscopic analyses for selected compounds. The most promising peptides were additionally evaluated for their activity against some representative veterinary microbial strains to compare with those from human strains. We identified novel analogues with interesting properties that make them attractive lead compounds.
引用
收藏
页码:1283 / 1290
页数:8
相关论文
共 51 条
[1]   A brief history of the antibiotic era: lessons learned and challenges for the future [J].
Aminov, Rustam I. .
FRONTIERS IN MICROBIOLOGY, 2010, 1
[2]   THE PROGRAM XEASY FOR COMPUTER-SUPPORTED NMR SPECTRAL-ANALYSIS OF BIOLOGICAL MACROMOLECULES [J].
BARTELS, C ;
XIA, TH ;
BILLETER, M ;
GUNTERT, P ;
WUTHRICH, K .
JOURNAL OF BIOMOLECULAR NMR, 1995, 6 (01) :1-10
[3]   COHERENCE TRANSFER BY ISOTROPIC MIXING - APPLICATION TO PROTON CORRELATION SPECTROSCOPY [J].
BRAUNSCHWEILER, L ;
ERNST, RR .
JOURNAL OF MAGNETIC RESONANCE, 1983, 53 (03) :521-528
[4]   Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria? [J].
Brogden, KA .
NATURE REVIEWS MICROBIOLOGY, 2005, 3 (03) :238-250
[5]  
Butaye P., 2015, ANTIMICROBIAL RESIST, P1
[6]   A different molecular mechanism underlying antimicrobial and hemolytic actions of temporins A and L [J].
Carotenuto, Alfonso ;
Malfi, Stefania ;
Saviello, Maria Rosaria ;
Campiglia, Pietro ;
Gomez-Monterrey, Isabel ;
Mangoni, Maria Luisa ;
Gaddi, Ludovica Marcellini Hercolani ;
Novellino, Ettore ;
Grieco, Paolo .
JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (08) :2354-2362
[7]   Rational design of α-helical antimicrobial peptides with enhanced activities and specificity/therapeutic index [J].
Chen, YX ;
Mant, CT ;
Farmer, SW ;
Hancock, REW ;
Vasil, ML ;
Hodges, RS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (13) :12316-12329
[8]   Origins and Evolution of Antibiotic Resistance [J].
Davies, Julian ;
Davies, Dorothy .
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 2010, 74 (03) :417-+
[9]   Annual Report of the Chief Medical Officer: infection and the rise of antimicrobial resistance [J].
Davies, Sally C. ;
Fowler, Tom ;
Watson, John ;
Livermore, David M. ;
Walker, David .
LANCET, 2013, 381 (9878) :1606-1609
[10]   NMRPIPE - A MULTIDIMENSIONAL SPECTRAL PROCESSING SYSTEM BASED ON UNIX PIPES [J].
DELAGLIO, F ;
GRZESIEK, S ;
VUISTER, GW ;
ZHU, G ;
PFEIFER, J ;
BAX, A .
JOURNAL OF BIOMOLECULAR NMR, 1995, 6 (03) :277-293