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Titolo:
Phage randomization in a charybdotoxin scaffold leads to CD4-mimetic recognition motifs that bind HIV-1 envelope through non-aromatic sequences
Autore:
Li, C; Dowd, CS; Zhang, W; Chaiken, IM;
Indirizzi:
Univ Penn, Stellar Chance Labs 909, Dept Med, Sch Med, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 , Sch Med, Philadelphia, PA 19104 USA
Titolo Testata:
JOURNAL OF PEPTIDE RESEARCH
fascicolo: 6, volume: 57, anno: 2001,
pagine: 507 - 518
SICI:
1397-002X(200106)57:6<507:PRIACS>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS TYPE-1; CONFORMATIONAL-CHANGES; DISPLAY LIBRARIES; SCORPION TOXINS; SOLUBLE CD4; RECEPTOR; GP120; GLYCOPROTEIN; ANTIBODY; SITE;
Keywords:
CD4; charybdotoxin; gp120; HIV-1; phage display;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Chaiken, IM Univ Penn, Stellar Chance Labs 909, Dept Med, Sch Med, 422 Curie Blvd, Philadelphia, PA 19104 USA Univ Penn 422 Curie Blvd Philadelphia PA USA 19104 A 19104 USA
Citazione:
C. Li et al., "Phage randomization in a charybdotoxin scaffold leads to CD4-mimetic recognition motifs that bind HIV-1 envelope through non-aromatic sequences", J PEPT RES, 57(6), 2001, pp. 507-518

Abstract

Binding of HIV-1 gp120 to T-cell receptor CD4 initiates conformational changes in the viral envelope that trigger viral entry into host cells. Phage epitope randomization of a p-turn loop of a charybdotoxin-based miniproteinscaffold was used to identify peptides that can bind gp120 and block the gp120-CD4 interaction. We describe here the display of the charybdotoxin scaffold on the filamentous phage FUSE5, its use to construct a p-turn library, and miniprotein sequences identified through library panning with immobilized Env gp120. Competition enzyme-linked immunosorbent assay (ELISA) identified high-frequency phage selectants for which specific gp120 binding was competed by sCD4. Several of these selectants contain hydrophobic residues in place of the Phe that occurs in the gp120-binding B-turns of both CD4 and previously identified scorpion toxin CD4 mimetics. One of these selectants, denoted TXM[(24)GQTL(27)], contains GQTL in place of the CD4 beta -turn sequence (40)QGSF(43) TXM[(24)GQTL(24)] peptide was prepared using solid-phase chemical synthesis, its binding to gp120 demonstrated by optical biosensor kinetics analysis and its affinity for the CD4 binding site of gp120 confirmed by competition ELISA. The results demonstrate that aromatic-less loop-containing CD4 recognition mimetics can be formed with detectable envelope protein binding within a p-turn of the charybdotoxin miniprotein scaffold. The results of this work establish a methodology for phage display of a charybdotoxin miniprotein scaffold and point to the potential value of phage-based epitope randomization of this miniprotein for identifying novel CD4mimetics. The latter are potentially useful in deconvoluting structural determinants of CD4-HIV envelope recognition and possibly in designing antagonists of viral entry.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 22:54:14