title: Design and evaluation of antiretroviral peptides corresponding to the C-terminal heptad repeat region (C-HR) of human immunodeficiency virus type 1 envelope glycoprotein gp41.
abstract: Two alpha-helical heptad repeats, N-HR and C-HR, located in the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41, play an important role in membrane fusion by forming a 6-helix bundle. C34, a peptide mimicking C-HR, inhibits the formation of the 6-helix bundle; thus, it has potential as a novel antiretroviral compound. In order to improve the inhibitory effect of C34 on HIV-1 replication, we designed new C34-derived peptides based on computational analysis of the stable conformation of the 6-helix bundle. Newly designed peptides showed a stronger inhibitory effect on the replication of recombinant viruses containing CRF01_AE, subtype B or subtype C Env than C34 or a fusion inhibitor, T-20. In addition, these peptides inhibited the replication of a T-20-resistant virus. We propose that these peptides could be applied to develop novel antiretroviral compounds to inhibit the replication of various subtypes of HIV-1 as well as of T-20-resistant variants.
authors.affiliation: Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI)(2), Nonthaburi, Thailand.
authors.forename: Bongkot
authors.initials: B
authors.lastname: Soonthornsata
authors.forename: Yu-Shi
authors.initials: YS
authors.lastname: Tian
authors.forename: Piraporn
authors.initials: P
authors.lastname: Utachee
authors.forename: Sompong
authors.initials: S
authors.lastname: Sapsutthipas
authors.forename: Panasda
authors.initials: P
authors.lastname: Isarangkura-na-Ayuthaya
authors.forename: Wattana
authors.initials: W
authors.lastname: Auwanit
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takagi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ikuta
authors.forename: Pathom
authors.initials: P
authors.lastname: Sawanpanyalert
authors.forename: Norihito
authors.initials: N
authors.lastname: Kawashita
authors.forename: Masanori
authors.initials: M
authors.lastname: Kameoka
mesh_terms: D000595:Amino Acid Sequence; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D015195:Drug Design; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D014779:Virus Replication / Q000187:drug effects
chemical_list: D044966:Anti-Retroviral Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D010455:Peptides; C407149:peptide C34