PMID- 38479167
OWN - NLM
STAT- MEDLINE
DCOM- 20240408
LR  - 20240408
IS  - 1768-3254 (Electronic)
IS  - 0223-5234 (Linking)
VI  - 269
DP  - 2024 Apr 5
TI  - Improving Anti-HIV activity and pharmacokinetics of enfuvirtide (T20) by 
      modification with oligomannose.
PG  - 116299
LID - S0223-5234(24)00179-X [pii]
LID - 10.1016/j.ejmech.2024.116299 [doi]
AB  - Dendritic cells (DCs) play a pivotal role in controlling HIV-1 infections of 
      CD4(+) T cells. DC-SIGN, which is expressed on the surface of DCs, efficiently 
      captures HIV-1 virions by binding to the highly mannosylated membrane protein, 
      gp120, and then the DCs transport the virus to target T cells in lymphoid organs. 
      This study explored the modification of T20, a peptide inhibitor of HIV-1 fusion, 
      by conjugation of the N-terminus with varying sizes of oligomannose, which are 
      DC-SIGN-specific carbohydrates, aiming to create dual-targeting HIV inhibitors. 
      Mechanistic studies indicated the dual-target binding of the conjugates. 
      Antiviral assays demonstrated that N-terminal mannosylation of T20 resulted in 
      increased inhibition of the viral infection of TZM-b1 cells (EC(50) = 0.3-0.8 vs. 
      1.4 nM). Pentamannosylated T20 (M5-T20) exhibited a stronger inhibitory effect on 
      virus entry into DC-SIGN+ 293T cells compared with T20 (67% vs. 50% inhibition at 
      500 muM). M5-T20 displayed an extended half-life in rats relative to T20 (T(1/2): 
      8.56 vs. 1.64 h, respectively). These conjugates represent a potential new 
      treatment for HIV infections with improved antiviral activity and 
      pharmacokinetics, and this strategy may prove useful in developing dual-target 
      inhibitors for other pathogens that require DC-SIGN involvement for infection.
CI  - Copyright (c) 2024 Elsevier Masson SAS. All rights reserved.
FAU - Cheng, Shuihong
AU  - Cheng S
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing, 100101, 
      China; Savaid Medical School, University of Chinese Academy of Sciences, Huairou 
      district, Beijing, 101408, China.
FAU - Xu, Mingyue
AU  - Xu M
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing, 100101, 
      China; Savaid Medical School, University of Chinese Academy of Sciences, Huairou 
      district, Beijing, 101408, China.
FAU - Li, Mingli
AU  - Li M
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing, 100101, 
      China; Savaid Medical School, University of Chinese Academy of Sciences, Huairou 
      district, Beijing, 101408, China.
FAU - Feng, Yong
AU  - Feng Y
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing, 100101, 
      China; Savaid Medical School, University of Chinese Academy of Sciences, Huairou 
      district, Beijing, 101408, China.
FAU - He, Lin
AU  - He L
AD  - National Key Laboratory of Intelligent Tracking and Forecasting for Infectious 
      Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for 
      Disease Control and Prevention, Beijing, 102206, China.
FAU - Liu, Tong
AU  - Liu T
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing, 100101, 
      China; Savaid Medical School, University of Chinese Academy of Sciences, Huairou 
      district, Beijing, 101408, China.
FAU - Ma, Liying
AU  - Ma L
AD  - National Key Laboratory of Intelligent Tracking and Forecasting for Infectious 
      Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for 
      Disease Control and Prevention, Beijing, 102206, China. Electronic address: 
      mal@chinaaids.cn.
FAU - Li, Xuebing
AU  - Li X
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing, 100101, 
      China; Savaid Medical School, University of Chinese Academy of Sciences, Huairou 
      district, Beijing, 101408, China. Electronic address: lixb@im.ac.cn.
LA  - eng
PT  - Journal Article
DEP - 20240308
PL  - France
TA  - Eur J Med Chem
JT  - European journal of medicinal chemistry
JID - 0420510
RN  - 19OWO1T3ZE (Enfuvirtide)
RN  - 0 (HIV Fusion Inhibitors)
RN  - 0 (Peptide Fragments)
RN  - 0 (HIV Envelope Protein gp41)
SB  - IM
MH  - Animals
MH  - Rats
MH  - Enfuvirtide/pharmacology/metabolism
MH  - *HIV Infections
MH  - *HIV Fusion Inhibitors/pharmacology/metabolism
MH  - Peptide Fragments/pharmacology/metabolism
MH  - HIV Envelope Protein gp41/metabolism
MH  - *HIV-1
OTO - NOTNLM
OT  - DC-SIGN
OT  - Dendritic cells (DCs)
OT  - Dual-targeted inhibition
OT  - Glycopeptide
OT  - HIV-1 infection
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2024/03/14 00:43
MHDA- 2024/04/08 06:43
CRDT- 2024/03/13 19:08
PHST- 2024/01/11 00:00 [received]
PHST- 2024/02/25 00:00 [revised]
PHST- 2024/03/01 00:00 [accepted]
PHST- 2024/04/08 06:43 [medline]
PHST- 2024/03/14 00:43 [pubmed]
PHST- 2024/03/13 19:08 [entrez]
AID - S0223-5234(24)00179-X [pii]
AID - 10.1016/j.ejmech.2024.116299 [doi]
PST - ppublish
SO  - Eur J Med Chem. 2024 Apr 5;269:116299. doi: 10.1016/j.ejmech.2024.116299. Epub 
      2024 Mar 8.