Non‐natural CBP2 binding peptides and peptomers modulate carcinoma cell adhesion and invasion

Abstract

A combinatorial approach that utilized a repertoire of bacteriophage-peptides has identified a number of non-natural CBP2 binding peptides. Moreover, co-localization of some of these peptides with CBP2 in a number of tumor cell lines demonstrated that the peptides were directed to an intracellular location spatially coincident with the normal distribution of CBP2 [Sauk et al., 2000]. From among these sequences WHYPWFQNWAMA and LDSRYSLQAAMY were the most effective CBP2 binding peptides and best fulfilled the combinatorial motif containing deep hydrophobic pockets. When the hydropathic profiles of collagen alpha1(IV) and alpha2 (IV) were compared with these dodecapeptides, the hydropathic profiles of WHYPWFQNWAMA and LDSRYSLQAAMY closely matched those of alpha1(IV) 414-452 and alpha1(IV)531-543. These peptides were shown to be functional peptidomimics and possessed the ability to alter cell adhesion and invasion of human squamous cell carcinoma cell lines. Peptomers were formed of these non-natural peptides to explore the role that a repetitive peptide may have on cell adhesion. The enhanced cell adhesion observed with the peptomers required both CBP2 antibodies and integrin antibodies for inhibition. The enhanced adhesion observed even in the face of combined antibody inhibition was consistent with such complexes possessing correspondingly slower dissociation rates. Thus, suggesting that peptomers may function in a like manner to multimeric peptide MHC complexes (tetramers) binding more than one cell receptor on a specific cell. These findings evoke both peptidomimics of native ligands and their peptomers as potential reagents by which to target tumor cells for chemotherapy, imaging, or retargeting viral vectors for gene therapy.

Effects of enamel matrix proteins on proliferation, differentiation and attachment of human alveolar osteoblasts

“…The method modified from Hebert (23) was performed to test for cell adhesion. In brief, 24‐well culture plates (Corning Inc.) were coated with 1 ml/well PBS containing EMPs (0, 50, 100 and 200 μg/ml) at 4 °C.…”

Effects of enamel matrix derivative and transforming growth factor‐β1 on human periodontal ligament fibroblasts

“…A cell adhesion assay was performed using the methods of Hebert et al (2001) with some modifications. Briefly, 24‐well culture plates were sensitized with 2 ml of PBS containing EMD, TGF‐ β 1, or EMD+TGF‐ β 1 at the same concentrations described above for 16 h at 4°C, and were subsequently washed three times with PBS.…”

Water-soluble polymers for targeted drug delivery to human squamous carcinoma of head and neck

“…This makes it a favorable candidate for targeted delivery of anticancer drugs (Sauk et al 2000). Several synthetic septapeptides and dodecapeptides of linear, helical or cyclic configuration have been identified by a combinatorial approach based on phage display, as effective ligands for highly enhanced and specific binding to Hsp47/CBP2 (Hebert et al 2001, Sauk et al 2000.…”

“…The synthesis, characterization and in vitro biological evaluation of N-(2-hydroxypropyl)-methacrylamide (HPMA) copolymer conjugate containing WHYPWFQNWAMA as the CBP2 binding peptide sequence (Hebert et al 2001), and the anticancer drug doxorubicin (Dox) as a model drug in the side chains is reported. The drug is attached to the polymer via a tetrapeptide spacer (GFLG), which is known to be degradable in the lysosomal compartment of the cells (reviewed in Putnam and Kopecek 1995).…”