Biselectivity of isoDGR Peptides for Fibronectin Binding Integrin Subtypes α5β1 and αvβ6: Conformational Control through Flanking Amino Acids

Bochen, Alexander; Marelli, Udaya Kiran; Otto, Elke; Pallarola, Diego; Mas‐Moruno, Carlos; Leva, Francesco Saverio Di; Boehm, Heike; Spatz, Joachim P.; Novellino, Ettore; Kessler, Horst; Marinelli, Luciana

doi:10.1021/jm301221x

Cited by 69 publications

(96 citation statements)

References 73 publications

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“…It is also worth mentioning that at higher concentrations of c(-RGDfK-), both curves reach similar low values, indicating negligible, unspecific binding of αvβ3 integrin to the substrates. Moreover, no binding inhibition was observed when a highly selective α5β1-antagonist, c(-phg-isoDGRk-) [63], was used, even at a concentration of 500 nM, demonstrating the specificity of the integrin binding process.…”

Section: Resultsmentioning

confidence: 97%

Focal adhesion stabilization by enhanced integrin-cRGD binding affinity

et al. 2017

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Abstract:In this study we investigate the impact of ligand presentation by various molecular spacers on integrin-based focal adhesion formation. Gold nanoparticles (AuNPs) arranged in hexagonal patterns were biofunctionalized with the same ligand head group, cyclic Arg-Gly-Asp [c(-RGDfX-)], but with different molecular spacers, each of which couples the head group to the gold. Aminohexanoic acid, polyethylene glycol (PEG) and polyproline spacers were used to vary the distance between the binding motif and the substrate, and thus the presentation of integrin binding on anchoring points. Adherent cells plated on nanopatterned surfaces with polyproline spacers for peptide immobilization could tolerate larger ligand spacing (162 nm) for focal adhesion formation, in comparison to cells on surfaces with PEG (110 nm) or aminohexanoic acid (62 nm) spacers. Due to the rigidity of the polyproline spacer, enhanced access to the ligand-binding site upon integrin-cRGD complex formation increases the probability of rebinding and decreases unbinding, as measured by fluorescence recovery after photobleaching (FRAP) analysis, compared to the analogues with aminohexanoic acid or PEGcontaining spacers. These findings indicate that focal adhesion formation may not only be stabilized upon tight integrin clustering, but also by tuning the efficiency of the exposure of the cRGD-based ligand to the integrin extracellular domains. Our studies clearly highlight the importance of ligand spatial presentation for regulating adhesion-dependent cell behavior, and provide a sound approach for studying cell signaling processes on nanometer-scale, engineered bioactive surfaces under chemical stimuli of varying intensities.

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Section: Resultsmentioning

confidence: 97%

Focal adhesion stabilization by enhanced integrin-cRGD binding affinity

et al. 2017

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“…43 However, the receptor recognition of isoDGR peptides highly depends on their structure. 13,44 Our objective was to evaluate the 3D structure, the chemo-stability as well as the in vitro interaction of these peptide models. For such study, cell adhesion was monitored as one of the most…”

Section: Cyclic Ngr-peptides Effect On Cell Adhesionmentioning

confidence: 99%

Development of Cyclic NGR Peptides with Thioether Linkage: Structure and Dynamics Determining Deamidation and Bioactivity

Enyedi¹,

Czajlik

Knapp³

et al. 2015

J. Med. Chem.

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Abstract AbstractIn drug targeting NGR-peptides recognized by CD13 receptors on tumor neovasculature have got improved interest. Here we present the synthesis and structure analysis of novel thioether linked cyclic NGR-peptides. We found that chemo-stability (resistance against spontaneous decomposition forming isoAsp and Asp derivatives) strongly depends both on sample handling conditions and structural properties. Significant correlation was found between chemo-stability and structural measures: e.g. NH Gly …CO Asn-sc distances. Side chain orientation of Asn is the key determining factor, if turned away from HN Gly chemo-stability increases. Structure stabilizing factors (e.g. H-bond(s)) lower their internal dynamics and thus macromolecules become even more resistant against spontaneous decomposition. Effect of cyclic NGR-peptides on cell adhesion was examined on A2058 melanoma cell lines. It was found that some of them gradually increased the cell adhesion with long term characteristics indicating the time-dependent formation of integrin binding isoAsp derivatives, responsible for the adhesion inducing effect.

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“…4C). αvβ3 is the main binding partner for c(RGDfK) with a 50-fold higher binding affinity compared to α5β1 integrin (Bochen et al, 2013). Therefore, these observations are in line with the low endogenous expression of αvβ3 in Jurkat cells (Nowlin et al, 1993).…”

Section: Evaluation Of Micro-structured Peptide Surfaces Via Cell Adhmentioning

confidence: 81%

Micro-structured peptide surfaces for the detection of high-affinity peptide–receptor interactions in living cells

Lipp¹,

Ji²,

Hager³

et al. 2015

Biosensors and Bioelectronics

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Biselectivity of isoDGR Peptides for Fibronectin Binding Integrin Subtypes α5β1 and αvβ6: Conformational Control through Flanking Amino Acids

Cited by 69 publications

References 73 publications

Focal adhesion stabilization by enhanced integrin-cRGD binding affinity

Focal adhesion stabilization by enhanced integrin-cRGD binding affinity

Development of Cyclic NGR Peptides with Thioether Linkage: Structure and Dynamics Determining Deamidation and Bioactivity

Micro-structured peptide surfaces for the detection of high-affinity peptide–receptor interactions in living cells

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