Structural Dissection of Crotalicidin, a Rattlesnake Venom Cathelicidin, Retrieves a Fragment with Antimicrobial and Antitumor Activity

被引:66
作者
Borges Falcao, Claudio [1 ,2 ]
Perez-Peinado, Clara [1 ]
de la Torre, Beatriz G. [1 ]
Mayol, Xavier [3 ]
Zamora-Carreras, Hector [4 ]
Angeles Jimenez, M. [4 ]
Radis-Baptista, Gandhi [1 ,2 ]
Andreu, David [1 ]
机构
[1] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona 08003, Spain
[2] Univ Fed Ceara, Lab Biochem & Biotechnol, Inst Marine Sci, BR-60455760 Fortaleza, Ceara, Brazil
[3] Inst Hosp Mar Invest Med, Programa Recerca Canc, Barcelona 08003, Spain
[4] CSIC, Inst Quim Fis Rocasolano, E-28006 Madrid, Spain
关键词
HOST-DEFENSE PEPTIDES; SNAKE CATHELICIDIN; CHEMICAL-SHIFT; NMR STRUCTURE; WEB SERVER; IN-VITRO; ANTIBACTERIAL; STRATEGIES; PROTEIN; IDENTIFICATION;
D O I
10.1021/acs.jmedchem.5b01142
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
In silico dissection of crotalicidin (Ctn), a cathelicidin from a South American pit viper, yielded fragments Ctn[1-14] and Ctn[15-34], which were tested to ascertain to what extent they reproduced the structure and activity of the parent peptide. NMR data showing Ctn to be alpha-helical at the N-terminus and unstructured at the C-terminus were matched by similar data from the fragments. The peptides were tested against Gram-positive and -negative bacteria and for toxicity against both tumor and healthy cells. Despite its amphipathic alpha-helical structure, Ctn[1-14] was totally inert toward bacteria or eukaryotic cells. In contrast, unstructured Ctn[15-34] replicated the activity of parent Ctn against Gram-negative bacteria and tumor cells while being significantly less toxic toward eukaryotic cells. This selectivity for bacteria and tumor cells, plus a stability to serum well above that of Ctn, portrays Ctn[15-34] as an appealing candidate for further development as an anti-infective or antitumor lead.
引用
收藏
页码:8553 / 8563
页数:11
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共 59 条
  • [21] New strategies and compounds for anti-infective treatment Editorial overview
    Hancock, Robert E. W.
    Sahl, Hans-Georg
    [J]. CURRENT OPINION IN MICROBIOLOGY, 2013, 16 (05) : 519 - 521
  • [22] Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies
    Hancock, Robert E. W.
    Sahl, Hans-Georg
    [J]. NATURE BIOTECHNOLOGY, 2006, 24 (12) : 1551 - 1557
  • [23] Serine protease mechanism and specificity
    Hedstrom, L
    [J]. CHEMICAL REVIEWS, 2002, 102 (12) : 4501 - 4523
  • [24] Design, NMR characterization and activity of a 21-residue peptide fragment of bacteriocin AS-48 containing its putative membrane interacting region
    Jiménez, MA
    Barrachi-Saccilotto, AC
    Valdivia, E
    Maqueda, M
    Rico, M
    [J]. JOURNAL OF PEPTIDE SCIENCE, 2005, 11 (01) : 29 - 36
  • [25] Characterization and Performance of Short Cationic Antimicrobial Peptide Isomers
    Juba, Melanie
    Porter, Devin
    Dean, Scott
    Gillmor, Susan
    Bishop, Barney
    [J]. BIOPOLYMERS, 2013, 100 (04) : 387 - 401
  • [26] MOLMOL: A program for display and analysis of macromolecular structures
    Koradi, R
    Billeter, M
    Wuthrich, K
    [J]. JOURNAL OF MOLECULAR GRAPHICS, 1996, 14 (01): : 51 - &
  • [27] Recommendations for the presentation of NMR structures of proteins and Nucleic Acids (Reprinted from Pure and Applied Chemistry, vol 70, pgs 117-142, 1998)
    Markley, JL
    Bax, A
    Arata, Y
    Hilbers, CW
    Kaptein, R
    Sykes, BD
    Wright, PE
    Wüthrich, K
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1998, 280 (05) : 933 - 952
  • [28] Neutrophil-derived serine proteases modulate innate immune responses
    Meyer-Hoffert, Ulf
    [J]. FRONTIERS IN BIOSCIENCE-LANDMARK, 2009, 14 : 3409 - +
  • [29] Disulfide Bonds versus Trp•••Trp Pairs in Irregular β-Hairpins: NMR Structure of Vammin Loop 3-Derived Peptides as a Case Study
    Mirassou, Yasmina
    Santiveri, Clara M.
    Jesus Perez de Vega, M.
    Gonzalez-Muniz, Rosario
    Angeles Jimenez, M.
    [J]. CHEMBIOCHEM, 2009, 10 (05) : 902 - 910
  • [30] Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense
    Murakami, M
    Lopez-Garcia, B
    Braff, M
    Dorschner, RA
    Gallo, RL
    [J]. JOURNAL OF IMMUNOLOGY, 2004, 172 (05) : 3070 - 3077