Single-domain antibodies that compete with the natural ligand fibroblast growth factor block the internalization of the fibroblast growth factor receptor 1 |
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Authors: | Veggiani Gianluca Ossolengo Giuseppe Aliprandi Marisa Cavallaro Ugo de Marco Ario |
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Institution: | aIFOM-IEO Campus, Via Adamello 16, 20139 Milano, Italy;bDept. Environmental Sciences, University of Nova Gorica (UNG), Vipavska 13, P.O. Box 301-SI-5000, Ro?na Dolina, Nova Gorica, Slovenia |
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Abstract: | Single-domain antibodies in VHH format specific for fibroblast growth factor receptor 1 (FGFR1) were isolated from a phage-display llama naïve library. In particular, phage elution in the presence of the natural receptor ligand fibroblast growth factor (FGF) allowed for the identification of recombinant antibodies that compete with FGF for the same region on the receptor surface. These antibodies posses a relatively low affinity for FGFR1 and were never identified when unspecific elution conditions favoring highly affine binders were applied to panning procedures. Two populations of competitive antibodies were identified that labeled specifically the receptor-expressing cells in immunofluorescence and recognize distinct epitopes. Antibodies from both populations effectively prevented FGF-dependent internalization and nuclear accumulation of the receptor in cultured cells. This achievement indicates that these antibodies have a capacity to modulate the receptor physiology and, therefore, constitute powerful reagents for basic research and a potential lead for therapeutic applications. |
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Keywords: | Abbreviations: FGF fibroblast growth factor FGFR1 fibroblast growth factor receptor 1 VHH heavy chain variable domain |
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