Immunoreactive Cycloimmunogen Design Based on Conformational Epitopes Derived from Human Immunodeficiency Virus Type 1 Coreceptors:Cyclic Dodecapeptides Mimic Undecapeptidyl Arches of Extracellular Loop-2 in Chemokine Receptor and Inhibit Human Immunodeficiency Virus Type 1 Infection

Authors: Misumi, Shogo; Takamune, Nobutoki; Shoji, Shozo

Source: Endocrine, Metabolic & Immune Disorders - Drug Targets, Volume 7, Number 2, June 2007 , pp. 141-152(12)

Publisher: Bentham Science Publishers

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Abstract:

Human immunodeficiency virus type 1 (HIV-1) requires a chemokine receptor (CCR5 or CXCR4) as a coreceptor not only for initiate viral entry but also protecting highly conserved neutralization epitopes from the attack of neutralizing antibodies. Over the past decade, many studies have provided new insights into the HIV entry mechanism and have focused on developing an effective vaccine strategy. However, to date, no vaccine that can provide protection from HIV-1 infection has been developed. One reason for the disappointing results has been the inability of current vaccine candidates to elicit a broadly reactive immunity to viral proteins such as the envelope (env) protein. Here, we propose that chemokine receptors are attractive targets of vaccine development because their structures are highly conserved and that our synthetic cycloimmunogens can mimic conformational-specific epitopes of undecapeptidyl arches (UPAs: R168-C178 in CCR5, N176-C186 in CXCR4) and be useful for HIV-1 novel vaccine development.

Keywords: Cycloimmunogen; HIV-1; conformational epitope; CCR5; CXCR4

Document Type: Research article

DOI: http://dx.doi.org/10.2174/187153007780832127

Publication date: 2007-06-01

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This journal is devoted to timely reviews of experimental and clinical studies in the field of endocrine, metabolic, and immune disorders. Specific emphasis is placed on humoral and cellular targets for natural, synthetic, and genetically engineered drugs that enhance or impair endocrine, metabolic, and immune parameters and functions. Topics related to the neuroendocrine-immune axis are given special emphasis in view of the growing interest in stress-related, inflammatory, autoimmune, and degenerative disorders.

Immunoreactive Cycloimmunogen Design Based on Conformational Epitopes Derived from Human Immunodeficiency Virus Type 1 Coreceptors:Cyclic Dodecapeptides Mimic Undecapeptidyl Arches of Extracellular Loop-2 in Chemokine Receptor and Inhibit Human Immunodeficiency Virus Type 1 Infection

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