Peptide Ligands for Integrin .alpha.v.beta.3 Selected from Random Phage Display Libraries

Healy, Judith M.; Murayama, Ohoshi; Maeda, Tatsuya; Yoshino, Kazuhiro; Sekiguchi, Kiyotoshi; Kikuchi, Masakazu

doi:10.1021/bi00012a012

Cited by 119 publications

(75 citation statements)

References 40 publications

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“…Although phage display was originally developed to identify antibody epitopes, phage display libraries are now widely used to identify peptide ligands to various proteins and other biomolecules (Goodson et al, 1994;Healy et al, 1995;Koivunen et al, 1993;Koivunen et al, 2001). Phage display is by no means limited to biological targets as peptides binding to semiconducting and magnetic materials can be isolated as well (Mao et al, 2004;Whaley et al, 2000).…”

Section: Applications Of Peptide Displaymentioning

confidence: 99%

Gelatinase-mediated migration and invasion of cancer cells

Björklund

Koivunen

2005

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

465

609

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Section: Applications Of Peptide Displaymentioning

confidence: 99%

Gelatinase-mediated migration and invasion of cancer cells

Björklund

Koivunen

2005

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

465

609

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“…32 Negussie et al successfully developed a head-to-side chain cyclic NGR-peptide. 33 In the c[KNGRE]-NH 2 peptide the α-amino group of the N-terminus and the side chain carboxyl group of Glu were attached by using on resin cyclization. The resulted ring size of the 17-atom-containing macrocycle is identical to that of c [CNGRC] with disulfide bond.…”

Section: Efficient Development Of Disulfide Bridge Containing Cyclic mentioning

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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“…This conclusion is supported by our RNAi knockdown studies. Incorporation of NGR-containing Pt(IV) conjugates 3a/3b may also be mediated in part by integrin α v β 3 , because this integrin binds NGR peptides, albeit with lower affinity than their RGD analogues (19). APN does not appear to be solely responsible for recognition of 3a/3b given that the IC 50 values were comparable in BCE and HMVEC despite differences in their APN/CD13 expression levels ( Table 1).…”

Section: Integrinsmentioning

confidence: 99%

Conjugated Platinum(IV)−Peptide Complexes for Targeting Angiogenic Tumor Vasculature

et al. 2007

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The integrins α v β 3 and α v β 5 and the membrane-spanning surface protein aminopeptidase-N (APN) are highly expressed in tumor-induced angiogenesis, making them attractive targets for therapeutic intervention. Both integrins and APN recognize a broad range of peptides containing RGD (ArgGly-Asp) and NGR (Asn-Gly-Arg) motifs, respectively. Here, we describe the design, synthesis, and characterization of a series of mono-and difunctionalized platinum(IV) complexes in which a conjugated peptide motif, containing either RGD, CRGDC, (RGDfK)c or NGR, is appended as a 'tumor-homing device' to target tumor endothelial cells selectively over healthy cells. Platinum(IV)-peptide complexes with non-specific amino acids or peptide moieties were prepared as controls. Concentration-response curves of these compounds were evaluated against primary proliferating endothelial cells and tumor cell lines and compared to those of cisplatin, a well-described platinumbased chemotherapeutic agent. The Pt(IV)-RGD conjugates were highly and specifically cytotoxic to α v β 3 and α v β 5 containing cell lines, approaching the activity of cisplatin. The Pt(IV)-NGR complexes were less active than Pt(IV)-RGD-containing compounds but more active than nonspecific Pt-peptide controls. Integrin α v β 3 mediated, at least in part, the anti-proliferative effect of an Pt(IV)-RGD conjugate, as demonstrated by a decreased inhibitory response when endothelial cells were either (1) incubated with an excess of α v β 3 /α v β 3 -specific RGD pentapeptides, or (2) transfected with RNAi for β 3 , but not β 1 , integrins. These results suggest a rational approach to improved chemotherapy with Pt(IV)-peptide conjugates by selective drug delivery to the tumor compartment.

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Peptide Ligands for Integrin .alpha.v.beta.3 Selected from Random Phage Display Libraries

Cited by 119 publications

References 40 publications

Gelatinase-mediated migration and invasion of cancer cells

Gelatinase-mediated migration and invasion of cancer cells

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

Conjugated Platinum(IV)−Peptide Complexes for Targeting Angiogenic Tumor Vasculature

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