Inhibition of hiv-1 infection by synthetic peptide analogues derived from the nh2-Terminal extracellular region of gpr1

Ikeda, Kiyoshi; Konishi, Koji; Sato, Masayuki; Hoshino, Hiroo; Tanaka, Kiyoshi

doi:10.1016/s0960-894x(01)00503-0

Bioorganic & Medicinal Chemistry Letters

2001

DOI: 10.1016/s0960-894x(01)00503-0

|View full text |Cite

Inhibition of hiv-1 infection by synthetic peptide analogues derived from the nh2-Terminal extracellular region of gpr1

Kiyoshi Ikeda

Koji Konishi

Masayuki Sato

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2004

2005

Publication Types

Select...

Article2

Relationship

Self Cite2

Independent0

Authors

Journals

Cited by 2 publications

(1 citation statement)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…12) We designed compounds with non-peptide spacers such as a benzene ring in place of the Ala-Ala-Ala sequence of the peptide moiety of CCR5. As part of a program aimed at the development of new HIV-1 inhibitors, [13][14][15][16][17][18] we would like to report the design and synthesis of CCR5 peptide mimics derived from the first extracellular loop of CCR5 bearing non-peptide spacers in place of AlaAla-Ala sequence in the peptide moiety for prevention of HIV-1 infection based on a strategy of binding to gp120.…”

mentioning

confidence: 99%

Synthesis and Biological Evaluation of Peptide Mimics Derived from First Extracellular Loop of CCR5 toward HIV-1

Ikeda

Ishii

Konishi

et al. 2004

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

The chemokine receptor CCR5, a member of the seventransmembrane G-protein coupled family of receptors, 1) has been identified as a primary co-receptor with CD4 by which macrophage tropic human immunodeficiency virus type-1 (HIV-1) strains infect their host cells.2) Since the discovery of CCR5 as a co-receptor with CD4 for HIV-1 cell entry, there has been interest in discovering small molecule CCR5 antagonists [3][4][5][6] as well as CXCR4 antagonists 7) and HIV-1 protease inhibitors 8) as potential agents for the treatment of HIV-1 infection.The entry of HIV-1 to cells involves the binding of the trimeric viral envelope glycoprotein gp120/gp41 to cell surface receptor CD4 and chemokine co-receptor CXCR4 or CCR5, which triggers conformational changes in the envelope proteins. Gp120 then dissociates from gp41, allowing for the fusion peptides to be inserted into the target membrane and the pre-hairpin configuration of the ectodomain to form.9-11) Regulation of CCR5 number on cells is important in determining the infection rate by HIV-1. Therefore, CCR5 is a highly valued target for the treatment of HIV-1 infection.It was demonstrated that the Gly-Gly-Gly sequence of the peptide moiety in lipopeptides could be replaced with a nonpeptide spacer.12) We designed compounds with non-peptide spacers such as a benzene ring in place of the Ala-Ala-Ala sequence of the peptide moiety of CCR5. As part of a program aimed at the development of new HIV-1 inhibitors, [13][14][15][16][17][18] we would like to report the design and synthesis of CCR5 peptide mimics derived from the first extracellular loop of CCR5 bearing non-peptide spacers in place of AlaAla-Ala sequence in the peptide moiety for prevention of HIV-1 infection based on a strategy of binding to gp120. Results and DiscussionIn the amino acid sequence of the N-terminal domain of CCR5, we chose the region of Tyr 89 -Gly 97 including alanine tripeptide. The peptide of natural type peptide 1 and its mimicking peptides 2a-c consisting of unnatural-type amino acids derived from aminophenol as the spacer unit were prepared. First, the nona-peptide 1 was synthesized manually by a stepwise liquid-phase procedure. The synthesis of 2a-c is shown in Chart 2. Aminophenoxyacetates 3a-c as spacers were prepared from the corresponding nitrophenols and tertbutyl bromoacetate. 19,20) Coupling of compounds 3a-c with 9-fluorenylmethoxycarbonyl (Fmoc)-Tyr(Bn) in the presence of 1-benzotriazoyloxy-tris-dimethylaminophosphonium hexafluorophosphate (BOP) and 1-hydroxy-1H-benzotriazole (HOBt) in N,N-dimethylformamide (DMF) gave compounds 4a-c in 72%, 73% and 86% yield, respectively. The deprotection of tert-butyl group of 4a-c with trifluoroacetic acid (TFA) afforded compounds 5a, 5b, and 5c in 71%, quant. and 93% yield, respectively. Compounds 5a-c were coupled with penta-peptide 6 in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCl) and HOBt in DMF to give compounds 7a-c in 78%, 81% and 95% yield, respectively. Finally, hydrogenolysis of compounds 7a-c cata...

show abstract

mentioning

confidence: 99%

Synthesis and Biological Evaluation of Peptide Mimics Derived from First Extracellular Loop of CCR5 toward HIV-1

Ikeda

Ishii

Konishi

et al. 2004

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

show abstract

The Synthetic Peptide Derived from the NH2-terminal Extracellular Region of an Orphan G Protein-coupled Receptor, GPR1, Preferentially Inhibits Infection of X4 HIV-1

Jinno-Oue

Shimizu

Soda

et al. 2005

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Several G protein-coupled receptors (GPCRs) serve as co-receptors for entry of human immunodeficiency virus type 1 (HIV-1) into target cells. Here we report that a synthetic peptide derived from the NH 2 -terminal extracellular region of an orphan GPCR, GPR1 (GPR1ntP-(1-27); MEDLEETLFEEFENYSYDLDYYSLESC), inhibited infection of not only an HIV-1 variant that uses GPR1 as a co-receptor, but also X4, R5, and R5X4 viruses. Among these HIV-1 strains tested, viruses that can utilize CXCR4 as their co-receptors were preferentially inhibited. Inhibition of early steps in X4 virus replication was also detected in the primary human peripheral blood lymphocytes. GPR1ntP-(1-27) directly interacted with recombinant X4 envelope glycoprotein (rgp120). This interaction was neither inhibited nor enhanced by the soluble CD4 (sCD4) but inhibited by the anti-third variable (V3) loop-specific monoclonal antibody and heparin known to bind to the V3 loop. Although the conformational changes in gp120, including the V3 loop, have been reported to be required for its interaction with a co-receptor after binding of gp120 to CD4, it has also been reported that the V3 loop is already exposed on the surface of virions before interaction with CD4.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Inhibition of hiv-1 infection by synthetic peptide analogues derived from the nh2-Terminal extracellular region of gpr1

Cited by 2 publications

References 14 publications

Synthesis and Biological Evaluation of Peptide Mimics Derived from First Extracellular Loop of CCR5 toward HIV-1

Synthesis and Biological Evaluation of Peptide Mimics Derived from First Extracellular Loop of CCR5 toward HIV-1

The Synthetic Peptide Derived from the NH2-terminal Extracellular Region of an Orphan G Protein-coupled Receptor, GPR1, Preferentially Inhibits Infection of X4 HIV-1

Contact Info

Product

Resources

About