title: 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.
authors.affiliation: Department of Pathology, University of Maryland, Baltimore 666 W. Baltimore Street Baltimore, Maryland 21201, USA.
authors.forename: C
authors.initials: C
authors.lastname: Hebert
authors.forename: R D
authors.initials: RD
authors.lastname: Coletta
authors.forename: K
authors.initials: K
authors.lastname: Norris
authors.forename: N
authors.initials: N
authors.lastname: Nikitakis
authors.forename: M
authors.initials: M
authors.lastname: Lopes
authors.forename: J J
authors.initials: JJ
authors.lastname: Sauk
mesh_terms: D001435:Bacteriophages / Q000378:metabolism; D001665:Binding Sites; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D002352:Carrier Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D006023:Glycoproteins; D006801:Humans; D009062:Mouth Neoplasms / Q000503:physiopathology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019151:Peptide Library; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D009842:Oligopeptides; D010446:Peptide Fragments; D019151:Peptide Library; C046289:colligin; D003094:Collagen