Ligand selectivity of a synthetic CXCR4 mimetic peptide

Gross, Andrea M.; Brox, Regine; Damm, Dominik; Tschammer, Nuška; Schmidt, Bárbara; Eichler, Jutta

doi:10.1016/j.bmc.2015.03.003

Cited by 10 publications

(7 citation statements)

References 32 publications

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“…We have generated a peptide that mimics the three ECLs of CXCR4 (Möbius et al, 2012 ) (Figure 8 A). This peptide, named CX4-M1, is able to discriminate between CXCR4- and CCR5-recognizing gp120 (Möbius et al, 2012 ) and V3-loop peptides mimicking the corresponding binding site on gp120 (Groß et al, 2013 ), and also inhibits HIV-1 infection of susceptible target cells in a CXCR4-specific manner (Möbius et al, 2012 ; Groß et al, 2015a ). Furthermore, CX4-M1 is recognized by the natural CXCR4-ligand, i.e., the chemokine CXCL12 (also called SDF-1α), as well as anti-CXCR4-antibodies (Groß et al, 2015a ).…”

Section: Protein Mimics In Biomedical Researchmentioning

confidence: 99%

Synthetic Peptides as Protein Mimics

Gross

Hashimoto

Sticht

et al. 2016

Front. Bioeng. Biotechnol.

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122

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The design and generation of molecules capable of mimicking the binding and/or functional sites of proteins represents a promising strategy for the exploration and modulation of protein function through controlled interference with the underlying molecular interactions. Synthetic peptides have proven an excellent type of molecule for the mimicry of protein sites because such peptides can be generated as exact copies of protein fragments, as well as in diverse chemical modifications, which includes the incorporation of a large range of non-proteinogenic amino acids as well as the modification of the peptide backbone. Apart from extending the chemical and structural diversity presented by peptides, such modifications also increase the proteolytic stability of the molecules, enhancing their utility for biological applications. This article reviews recent advances by this and other laboratories in the use of synthetic protein mimics to modulate protein function, as well as to provide building blocks for synthetic biology.

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Section: Protein Mimics In Biomedical Researchmentioning

confidence: 99%

Synthetic Peptides as Protein Mimics

Gross

Hashimoto

Sticht

et al. 2016

Front. Bioeng. Biotechnol.

Self Cite

122

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“…Cross‐resistance of b12‐H1H3‐resistant virus for b12, as well as that of b12‐resistant virus for b12‐H1H3, was evident as well, although less apparent, with 4.5‐fold and 5.6‐fold differences in IC 50 values between wt and resistant virus. As a control, we used a CXCR4 mimetic peptide (CX4‐M1), which binds to the coreceptor binding site of gp120 that does not overlap the b12 epitope. The neutralizing capacity of CX4‐M1 was largely unaffected by mutations in the b12‐ and b12‐H1H3‐resistant viruses, as demonstrated by the essentially identical IC 50 values of CX4‐M1—that is, 3.8, 6.8, and 4.1 μ m , respectively—against wt and the two resistant viruses (Table ), implying that the differences in neutralizing activity of b12 against wt and b12‐H1H3‐resistant virus, as well as of b12‐H1H3 against wt and b12‐resistant virus, respectively, signify real cross‐resistance.…”

Section: Resultsmentioning

confidence: 99%

“…The concept of mimicking protein binding sites, including sequentially discontinuous binding sites, through assembled synthetic peptides has been demonstrated for a range of diverse proteins, including the CD4 binding site of HIV‐1 gp120 and the extracellular domain of the HIV‐1 coreceptor CXCR4 …”

Section: Introductionmentioning

confidence: 99%

Peptide Paratope Mimics of the Broadly Neutralizing HIV‐1 Antibody b12

et al. 2017

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The broadly neutralizing HIV-1 antibody b12 recognizes the CD4 binding site of the HIV-1 envelope glycoprotein gp120 and efficiently neutralizes HIV-1 infections in vitro and in vivo. Based on the 3D structure of a b12⋅gp120 complex, we have designed an assembled peptide (b12-M) that presents the parts of the three heavy-chain complementarity-determining regions (CDRs) of b12, which contain the contact sites of the antibody for gp120. This b12-mimetic peptide, as well as a truncated peptide presenting only two of the three heavy-chain CDRs of b12, were shown to recognize gp120 in a similar manner to b12, as well as to inhibit HIV-1 infection, demonstrating functional mimicry of b12 by the paratope mimetic peptides.

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“…[20] Binding of P6-2 to the V3 loop would compete with coreceptor-V3 loop interaction, preventing attachment of the virus to the corecep-tor, and, consequently, entry into the cell. The V3 loop of X4 tropic HIV-1, which uses CXCR4 as the coreceptor, contacts the second extracellular loop (ECL2) of the receptor, which is also part of a CXCR4 mimetic peptide we have previously published, [19,21,22] and whose HIV-1 inhibitory activity is also based on interaction with the gp120 V3 loop. Interestingly, the CXCR4 ECL2 ( 182 DRYICDRFYPNDLWV 196 ) bears some resemblance with P6-2.…”

Section: Exploring the Molecular Mechanism Of Hiv-1 Inhibition By P6-2mentioning

confidence: 99%

Exploring Viral Interference Using Peptides: Molecular Determinants of HIV‐1 Inhibition by a Peptide Derived from Human Pegivirus‐1 Envelope Protein E2

et al. 2021

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Co-infection with the human pegivirus 1 (HPgV-1) often has a beneficial effect on disease progression in HIV-1-infected individuals. Several HPgV-1 proteins and peptides, including a 20-mer peptide (P6-2) derived from the N-terminal region of the HPgV-1 surface protein E2, have been associated with this phenomenon, which is referred to as viral interference. We identified the cysteine residues, the hydrophobic core tetrapeptide, as well as the C-terminal negative charge as key factors for the HIV-1 inhibitory activity of P6-2. Analysis of mutations in P6-2-resistant HIV-1 indicated a binding site for the peptide in the HIV-1 envelope glycoprotein gp120. In fact, P6-2 was shown to bind to soluble gp120, as well as to a peptide presenting the gp120 V3 loop. Furthermore, the HIV-1 inhibitory activity of P6-2 could be revoked by the V3 loop peptide, thus indicating a molecular mechanism that involves interaction of P6-2 with the gp120 V3 loop.

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Ligand selectivity of a synthetic CXCR4 mimetic peptide

Cited by 10 publications

References 32 publications

Synthetic Peptides as Protein Mimics

Synthetic Peptides as Protein Mimics

Peptide Paratope Mimics of the Broadly Neutralizing HIV‐1 Antibody b12

Exploring Viral Interference Using Peptides: Molecular Determinants of HIV‐1 Inhibition by a Peptide Derived from Human Pegivirus‐1 Envelope Protein E2

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