PMID- 38364308
OWN - NLM
STAT- MEDLINE
DCOM- 20240315
LR  - 20240315
IS  - 1520-4804 (Electronic)
IS  - 0022-2623 (Linking)
VI  - 67
IP  - 5
DP  - 2024 Mar 14
TI  - Glycan-Modified Peptides for Dual Inhibition of Human Immunodeficiency Virus 
      Entry into Dendritic Cells and T Cells.
PG  - 4225-4233
LID - 10.1021/acs.jmedchem.4c00116 [doi]
AB  - Dendritic cells (DCs) play a crucial role in HIV-1 infection of CD4+ T cells. 
      DC-SIGN, a lectin expressed on the surface of DCs, binds to the highly 
      mannosylated viral membrane protein gp120 to capture HIV-1 virions and then 
      transport them to target T cells. In this study, we modified peptide C34, an 
      HIV-1 fusion inhibitor, at different sites using different sizes of the 
      DC-SIGN-specific carbohydrates to provide dual-targeted HIV inhibition. The 
      dual-target binding was confirmed by mechanistic studies. Pentamannose-modified 
      C34 inhibited virus entry into both DC-SIGN+ 293T cells (52%-71% inhibition at 
      500 muM) and CD4+ TZM-b1 cells (EC(50) = 0.7-1.7 nM). One conjugate, NC-M5, showed 
      an extended half-life relative to C34 in rats (T(1/2): 7.8 vs 1.02 h). These 
      improvements in antiviral activity and pharmacokinetics have potential for HIV 
      treatment and the development of dual-target inhibitors for pathogens that 
      require the involvement of DC-SIGN for infection.
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.
AD  - 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.
AD  - 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.
AD  - Savaid Medical School, University of Chinese Academy of Sciences, Huairou 
      district, Beijing 101408, 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.
AD  - 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, People's Republic of 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.
AD  - 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, People's Republic of China.
FAU - Li, Xuebing
AU  - Li X
AUID- ORCID: 0000-0001-8903-9793
AD  - CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of 
      Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, 
      China.
AD  - Savaid Medical School, University of Chinese Academy of Sciences, Huairou 
      district, Beijing 101408, China.
LA  - eng
PT  - Journal Article
DEP - 20240216
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Lectins, C-Type)
RN  - 0 (Polysaccharides)
RN  - 0 (HIV Envelope Protein gp120)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Rats
MH  - Cell Line
MH  - *HIV-1/metabolism
MH  - *HIV Infections
MH  - Lectins, C-Type/metabolism
MH  - Dendritic Cells/metabolism
MH  - Polysaccharides/pharmacology
MH  - HIV Envelope Protein gp120/metabolism
EDAT- 2024/02/16 18:43
MHDA- 2024/03/15 06:43
CRDT- 2024/02/16 17:43
PHST- 2024/03/15 06:43 [medline]
PHST- 2024/02/16 18:43 [pubmed]
PHST- 2024/02/16 17:43 [entrez]
AID - 10.1021/acs.jmedchem.4c00116 [doi]
PST - ppublish
SO  - J Med Chem. 2024 Mar 14;67(5):4225-4233. doi: 10.1021/acs.jmedchem.4c00116. Epub 
      2024 Feb 16.