title: α-Helix peptides designed from EBV-gH protein display higher antigenicity and induction of monocyte apoptosis than the native peptide.
abstract: We tested the hypothesis that stabilizing α-helix of Epstein-Barr virus gH-derived peptide 11438 used for binding human cells will increase its biological activity. Non-stable α-helix of peptide 11438 was unfolded in an entropy-driven process, despite the opposing effect of the enthalpy factor. Adding and/or changing amino acids in peptide 11438 allowed the designing of peptides 33207, 33208 and 33210; peptides 33208 and 33210 displayed higher helical content due to a decreased unfolding entropy change as was determined by AGADIR, molecular dynamics and circular dichroism analysis. Peptides 33207, 33208 and 33210 inhibited EBV invasion of peripheral blood mononuclear cells and displayed epitopes more similar to native protein than peptide 11438; these peptides could be useful for detecting antibodies induced by native gH protein since they displayed high reactivity with anti-EBV antibodies. Anti-peptide 33207 antibodies showed higher reactivity with EBV than anti-peptide 11438 antibodies being useful for inducing antibodies against EBV. Anti-peptide 33210 antibodies inhibit EBV invasion of epithelial cells better than anti-peptide 11438 antibodies. Peptide 33210 bound to normal T lymphocytes and Raji cells stronger than peptide 11438 and also induced apoptosis of monocytes and Raji cells but not of normal T cells in a similar way to EBV-gH. Peptide 33210 inhibited the monocytes' development toward dendritic cells better than EBV and peptide 11438. In conclusion, stabilizing the α-helix in peptides 33208 and 33210 designed from peptide 11438 increased the antigenicity and the ability of the antibodies induced by peptides of inhibiting EBV invasion of host cells.
authors.affiliation: Fundacion Instituto de Inmunologia de Colombia, Bogotá, Colombia. murquiza@ucsd.edu
authors.forename: Mauricio
authors.initials: M
authors.lastname: Urquiza
authors.forename: Johanna
authors.initials: J
authors.lastname: Melo-Cardenas
authors.forename: Tatiana
authors.initials: T
authors.lastname: Guevara
authors.forename: Ignacia
authors.initials: I
authors.lastname: Echeverria
authors.forename: Isabel C
authors.initials: IC
authors.lastname: Rodriguez
authors.forename: Magnolia
authors.initials: M
authors.lastname: Vanegas
authors.forename: Mario
authors.initials: M
authors.lastname: Amzel
authors.forename: Manuel E
authors.initials: ME
authors.lastname: Patarroyo
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004854:Herpesvirus 4, Human / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D011817:Rabbits; D013816:Thermodynamics; D014764:Viral Proteins / Q000737:chemistry* / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D010455:Peptides; D014764:Viral Proteins
references.citation: J Exp Med. 1986 Dec 1;164(6):2049-60
references.pmid: 3491176
references.citation: Int J Cancer. 1987 Jan 15;39(1):25-9
references.pmid: 3025109
references.citation: J Virol. 1996 Aug;70(8):5557-63
references.pmid: 8764069
references.citation: Blood. 2004 Jun 15;103(12):4389-95
references.pmid: 14962897
references.citation: J Virol. 2000 Jul;74(14):6324-32
references.pmid: 10864642
references.citation: J Clin Invest. 1986 Aug;78(2):439-47
references.pmid: 3016028
references.citation: J Virol. 2005 Oct;79(19):12408-15
references.pmid: 16160168
references.citation: Int J Pept Protein Res. 1983 Jan;21(1):57-65
references.pmid: 6826283
references.citation: Proc Natl Acad Sci U S A. 1985 Aug;82(15):5131-5
references.pmid: 2410914
references.citation: J Virol. 1988 Jul;62(7):2366-72
references.pmid: 2836619
references.citation: J Pathol. 2002 Aug;197(5):684-8
references.pmid: 12210090
references.citation: Cell. 1987 Jul 17;50(2):203-13
references.pmid: 3036369
references.citation: Biochem Biophys Res Commun. 1983 Dec 16;117(2):479-85
references.pmid: 6661238
references.citation: J Virol. 1998 Jul;72(7):5552-8
references.pmid: 9621012
references.citation: J Virol. 1997 Jun;71(6):4657-62
references.pmid: 9151859
references.citation: Biochemistry. 1981 Jan 6;20(1):33-7
references.pmid: 7470476
references.citation: Science. 1984 Jul 6;225(4657):63-6
references.pmid: 6328661
references.citation: J Virol. 1989 Dec;63(12):4998-5005
references.pmid: 2555536
references.citation: Biopolymers. 1997 Apr 15;41(5):495-509
references.pmid: 9095674
references.citation: J Virol. 1999 Mar;73(3):2115-25
references.pmid: 9971794
references.citation: Eur J Immunol. 1995 Apr;25(4):877-83
references.pmid: 7737288
references.citation: Blood. 2002 May 15;99(10):3725-34
references.pmid: 11986229
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20464-9
references.pmid: 19920174
references.citation: J Immunol. 1982 Dec;129(6):2532-5
references.pmid: 6292290
references.citation: Biochem Biophys Res Commun. 2004 Jun 18;319(1):221-9
references.pmid: 15158465
references.citation: Proc Natl Acad Sci U S A. 1968 Jan;59(1):94-101
references.pmid: 5242134
references.citation: Nat Med. 2002 Jun;8(6):594-9
references.pmid: 12042810
references.citation: Cell. 1989 Feb 10;56(3):369-77
references.pmid: 2464439
references.citation: Methods Enzymol. 1996;266:540-53
references.pmid: 8743705
references.citation: Int J Cancer. 1974 Nov 15;14(5):580-8
references.pmid: 4142471