Substitution of the Arginine/Leucine Residues in Apidaecin Ib with Peptoid Residues: Effect on Antimicrobial Activity, Cellular Uptake, and Proteolytic Degradation

被引:33
作者
Gobbo, Marina [1 ]
Benincasa, Monica [2 ]
Bertoloni, Giulio [3 ]
Biondi, Barbara [4 ]
Dosselli, Ryan [5 ]
Papini, Emanuele [6 ,7 ]
Reddi, Elena [5 ]
Rocchi, Raniero [1 ]
Tavano, Regina [6 ,7 ]
Gennaro, Renato [2 ]
机构
[1] Univ Padua, Dept Chem Sci, I-35131 Padua, Italy
[2] Univ Trieste, Dept Life Sci, I-34127 Trieste, Italy
[3] Univ Padua, Dept Histol Microbiol & Med Biotechnol, I-35131 Padua, Italy
[4] CNR, Inst Biomol Chem, I-35131 Padua, Italy
[5] Univ Padua, Dept Biol, I-35121 Padua, Italy
[6] Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy
[7] Univ Padua, CRIBI, I-35121 Padua, Italy
关键词
PROLINE-RICH PEPTIDES; SOLID-PHASE SYNTHESIS; ANTIBACTERIAL PEPTIDES; MECHANISM; DELIVERY; MODE;
D O I
10.1021/jm900396a
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Several aspects of the mechanism of action of Pro-rich antimicrobial peptides, together with their low toxicity ill mammalian cells, make them good candidates for the development of new antibiotic agents. We investigated the effect induced in the insect antimicrobial peptide apidaecin Ib by the replacement of a single arginine/leucine residue witha N-substituted glycine. The resulting peptoid-peptide hybrids are more resistant to proteolysis and devoid of any significant cytotoxic activity, but moving the [NArg]residue from the N- to the C-terminal end of the molecule progressively reduces the antibacterial activity. Cell uptake experiments in E. coli cells suggest that the loss of antibacterial activity of [NArg(17)]apidaecin is a consequence of its inability to translocate into bacterial cells. Conversely, apidaecin and its peptoid-peptide hybrids are able to cross the plasma membrane ill eukaryotic cells and to diffuse in the cytosol, although their translocating ability is far less effective than that of other known cell permeant peptides.
引用
收藏
页码:5197 / 5206
页数:10
相关论文
共 43 条
[1]   A NOVEL LYSINE-PROTECTING PROCEDURE FOR CONTINUOUS-FLOW SOLID-PHASE SYNTHESIS OF BRANCHED PEPTIDES [J].
BYCROFT, BW ;
CHAN, WC ;
CHHABRA, SR ;
HONE, ND .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1993, (09) :778-779
[2]   APIDAECIN-TYPE PEPTIDE ANTIBIOTICS FUNCTION THROUGH A NON-POREFORMING MECHANISM INVOLVING STEREOSPECIFICITY [J].
CASTEELS, P ;
TEMPST, P .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 199 (01) :339-345
[3]   APIDAECINS - ANTIBACTERIAL PEPTIDES FROM HONEYBEES [J].
CASTEELS, P ;
AMPE, C ;
JACOBS, F ;
VAECK, M ;
TEMPST, P .
EMBO JOURNAL, 1989, 8 (08) :2387-2391
[4]   Lethal effects of apidaecin on Escherichia coli involve sequential molecular interactions with diverse targets [J].
Castle, M ;
Nazarian, A ;
Yi, SS ;
Tempst, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (46) :32555-32564
[5]  
Chan WC, 2000, PRACT APPROACH SER, V222, P41
[6]   Visualizing a correlation between siRNA localization, cellular uptake, and RNAi in living cells [J].
Chiu, YL ;
Ali, A ;
Chu, CY ;
Cao, H ;
Rana, TM .
CHEMISTRY & BIOLOGY, 2004, 11 (08) :1165-1175
[7]   Functional mapping of apidaecin through secondary structure correlation [J].
Dutta, Ranjna C. ;
Nagpal, Sushma ;
Salunke, Dinakar M. .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2008, 40 (05) :1005-1015
[8]   Potential peptide carriers:: Amphipathic proline-rich peptides derived from the n-terminal domain of γ-zein [J].
Fernández-Carneado, J ;
Kogan, MJ ;
Castel, S ;
Giralt, E .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (14) :1811-1814
[9]   Extending the applicability of carboxyfluorescein in solid-phase synthesis [J].
Fischer, R ;
Mader, O ;
Jung, G ;
Brock, R .
BIOCONJUGATE CHEMISTRY, 2003, 14 (03) :653-660
[10]   Pro-rich antimicrobial peptides from animals: Structure, biological functions and mechanism of action [J].
Gennaro, R ;
Zanetti, M ;
Benincasa, M ;
Podda, E ;
Miani, M .
CURRENT PHARMACEUTICAL DESIGN, 2002, 8 (09) :763-778